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Mendeliome v1.4072 HBD Zornitza Stark Marked gene: HBD as ready
Mendeliome v1.4072 HBD Zornitza Stark Gene: hbd has been classified as Green List (High Evidence).
Mendeliome v1.4072 Zornitza Stark Copied gene HBD from panel Red cell disorders
Mendeliome v1.4072 HBD Zornitza Stark gene: HBD was added
gene: HBD was added to Mendeliome. Sources: Expert Review Green,Yorkshire and North East GLH,NHS GMS,Wessex and West Midlands GLH,North West GLH,London South GLH
Mode of inheritance for gene: HBD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HBD were set to 27630894; 25490067
Phenotypes for gene: HBD were set to Thalassaemia, delta-; Thalassaemia due to Hb Lepore
Mendeliome v1.3909 THBD Zornitza Stark Phenotypes for gene: THBD were changed from {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926; Bleeding disorder to Thrombophilia 12 due to thrombomodulin defect, MIM# 614486
Mendeliome v1.3908 THBD Zornitza Stark Publications for gene: THBD were set to 29500241; 19625716; 25564403; 32634856
Mendeliome v1.3907 THBD Zornitza Stark edited their review of gene: THBD: Changed publications: 29500241, 19625716, 25564403, 32634856, 39841007, 34474479; Changed phenotypes: Thrombophilia 12 due to thrombomodulin defect, MIM# 614486
Mendeliome v1.3907 THBD Zornitza Stark edited their review of gene: THBD: Added comment: Association with bleeding disorders:

PMID 39841007: identified 8 THBD variants for 6 patients with a thrombotic (C175S, A282P, L433P, P501L, G502R, and P508L) and 2 patients with a bleeding (P260A and T478I) phenotypes from a large cohort. Functional evidence supporting pathogenicity only generated for two of the variants, functional effects of L433P and potentially C175S.

PMID 34474479: single individual with homozygous missense variant, c.793T>A (p.Cys265Ser) and potentially life-threatening bleeding events.; Changed rating: GREEN; Changed phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926, Thrombophilia 12 due to thrombomodulin defect, MIM# 614486
Mendeliome v1.3283 RHBDF2 Lucy Spencer reviewed gene: RHBDF2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency disease MONDO:0021094, RHBDF2-related; Mode of inheritance: None
Mendeliome v1.3283 RHBDF1 Lucy Spencer reviewed gene: RHBDF1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy MONDO:0005021, RHBDF1-related; Mode of inheritance: None
Mendeliome v1.1587 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Mendeliome v0.10757 RHBDF2 Zornitza Stark Marked gene: RHBDF2 as ready
Mendeliome v0.10757 RHBDF2 Zornitza Stark Gene: rhbdf2 has been classified as Green List (High Evidence).
Mendeliome v0.10757 RHBDF2 Zornitza Stark Phenotypes for gene: RHBDF2 were changed from to Tylosis with esophageal cancer, MIM# 148500; Immune dysregulation
Mendeliome v0.10756 RHBDF2 Zornitza Stark Publications for gene: RHBDF2 were set to
Mendeliome v0.10755 RHBDF2 Zornitza Stark Mode of inheritance for gene: RHBDF2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10754 RHBDF2 Zornitza Stark reviewed gene: RHBDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22265016, 22638770, 34937930; Phenotypes: Tylosis with esophageal cancer, MIM# 148500, Immune dysregulation; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6800 RHBDF1 Zornitza Stark Marked gene: RHBDF1 as ready
Mendeliome v0.6800 RHBDF1 Zornitza Stark Gene: rhbdf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6800 RHBDF1 Zornitza Stark Classified gene: RHBDF1 as Amber List (moderate evidence)
Mendeliome v0.6800 RHBDF1 Zornitza Stark Gene: rhbdf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6799 RHBDF1 Zornitza Stark gene: RHBDF1 was added
gene: RHBDF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHBDF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHBDF1 were set to 32870709
Phenotypes for gene: RHBDF1 were set to Dilated cardiomyopathy
Review for gene: RHBDF1 was set to AMBER
Added comment: Three families reported with homozygous variants in this gene and onset of DCM in infancy/childhood. Two of the families had the same truncating variant, indicative of founder effect, and one family had a homozygous missense variant.
Sources: Literature
Mendeliome v0.5501 THBD Bryony Thompson Classified gene: THBD as Green List (high evidence)
Mendeliome v0.5501 THBD Bryony Thompson Gene: thbd has been classified as Green List (High Evidence).
Mendeliome v0.5500 THBD Bryony Thompson reviewed gene: THBD: Rating: GREEN; Mode of pathogenicity: None; Publications: 32634856, 25564403, 32935436, 25049278, 27436851, 28267383, 10627464; Phenotypes: Thrombomodulin‐associated coagulopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3801 THBD Zornitza Stark Phenotypes for gene: THBD were changed from {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926 to {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926; Bleeding disorder
Mendeliome v0.3800 THBD Zornitza Stark Publications for gene: THBD were set to 29500241; 19625716
Mendeliome v0.3799 THBD Zornitza Stark edited their review of gene: THBD: Added comment: Variants in this gene have also been linked to thrombophilia. Two families reported with a bleeding disorder, both variants located in the transmembrane domain.; Changed publications: 29500241, 19625716, 25564403, 32634856; Changed phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926, Bleeding disorder
Mendeliome v0.2146 THBD Zornitza Stark Marked gene: THBD as ready
Mendeliome v0.2146 THBD Zornitza Stark Gene: thbd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2146 THBD Zornitza Stark Phenotypes for gene: THBD were changed from to {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926
Mendeliome v0.2145 THBD Zornitza Stark Publications for gene: THBD were set to
Mendeliome v0.2144 THBD Zornitza Stark Mode of inheritance for gene: THBD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2143 THBD Zornitza Stark Classified gene: THBD as Amber List (moderate evidence)
Mendeliome v0.2143 THBD Zornitza Stark Gene: thbd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2142 THBD Zornitza Stark reviewed gene: THBD: Rating: AMBER; Mode of pathogenicity: None; Publications: 29500241, 19625716; Phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.0 THBD Zornitza Stark gene: THBD was added
gene: THBD was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: THBD was set to Unknown
Mendeliome v0.0 RHBDF2 Zornitza Stark gene: RHBDF2 was added
gene: RHBDF2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RHBDF2 was set to Unknown