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| Fetal anomalies v2.0 | COL10A1 | Gene migrated from ENSG00000123500 to ENSG00000123500 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.477 | COL10A1 | Zornitza Stark Publications for gene: COL10A1 were set to 15880705; 31633898 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.476 | COL10A1 | Zornitza Stark edited their review of gene: COL10A1: Changed publications: 15880705, 31633898, 31348255, 25542771 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.476 | COL10A1 |
Zornitza Stark changed review comment from: Note: Gene reviews also notes severe lethal phenotypes in recessive inheritance where parents were only mildly affected, however only 2 unrelated families reported to date (PMID: 31633898). Both haploinsufficiency and dominant-negative mechanisms have been suggested to cause disease (OMIM, PMID: 15880705, PMID: 31633898). “Pathogenic variants in COL10A1 are clustered in the C-terminal non-collagenous (NC1) domain, which contains motifs required for normal assembly of the collagen trimer. Both missense and truncating (frameshift and nonsense) variants in COL10A1 cause collagen X protein misfolding during protein synthesis, resulting in a failure of trimerization and aggregation within the endoplasmic reticulum (ER) of hypertrophic chondrocytes. Resultant ER stress, activation of the unfolded protein response, and reduced levels of functional type X collagen in the growth plate cause chondrodysplasia and development of the SMCD phenotype [Rajpar et al 2009].” -> from Gene Reviews (PMID: 31633898). Some pathogenic missense also reported in the N-terminal signal peptide (Decipher), however please note that to date, no Gly-X-Y substitutions in the collagen triple helix repeats have yet been reported, pathogenic or otherwise.; to: Note: Gene reviews also notes severe lethal phenotypes in recessive inheritance where parents were only mildly affected, however only 2 unrelated families reported to date (PMID: 31633898). Both haploinsufficiency and dominant-negative mechanisms have been suggested to cause disease (OMIM, PMID: 15880705, PMID: 31633898). “Pathogenic variants in COL10A1 are clustered in the C-terminal non-collagenous (NC1) domain, which contains motifs required for normal assembly of the collagen trimer. Both missense and truncating (frameshift and nonsense) variants in COL10A1 cause collagen X protein misfolding during protein synthesis, resulting in a failure of trimerization and aggregation within the endoplasmic reticulum (ER) of hypertrophic chondrocytes. Resultant ER stress, activation of the unfolded protein response, and reduced levels of functional type X collagen in the growth plate cause chondrodysplasia and development of the SMCD phenotype [Rajpar et al 2009].” -> from Gene Reviews (PMID: 31633898). Some pathogenic missense also reported in the N-terminal signal peptide (Decipher). Note that unlike with other collagens, Gly-X-Y substitutions in the collagen triple helix repeats are very rarely reported as disease-causing, and may result in a milder phenotype (PMID 31348255; 25542771). These should be interpreted with caution. |
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| Fetal anomalies v0.565 | COL10A1 | Zornitza Stark Marked gene: COL10A1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.565 | COL10A1 | Zornitza Stark Gene: col10a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.565 | COL10A1 | Zornitza Stark Phenotypes for gene: COL10A1 were changed from SCHMID TYPE METAPHYSEAL CHONDRODYSPLASIA to Metaphyseal chondrodysplasia, Schmid type, MIM#156500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.564 | COL10A1 | Zornitza Stark Publications for gene: COL10A1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.563 | COL10A1 | Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.562 | COL10A1 | Zornitza Stark reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, MIM#156500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | COL10A1 |
Zornitza Stark gene: COL10A1 was added gene: COL10A1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: COL10A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: COL10A1 were set to SCHMID TYPE METAPHYSEAL CHONDRODYSPLASIA |
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