Curating the Clinical Genome 2024 ePoster Gallery-Deciphering the Collagen Code Navigating Variant Curation Complexities in Skeletal Disorders

Deciphering the Collagen Code Navigating Variant Curation Complexities in Skeletal Disorders

Pdf Summary

The text discusses genetic alterations in the COL2A1 gene, specifically focusing on truncating, missense, and in-frame indels in different regions of the gene. It highlights that truncating alterations in certain regions may lead to haploinsufficiency, while other alterations in the C-propeptide region can have a dominant negative effect. The document also provides information on the structure of COL2A1, COL1A1, and COL1A2 proteins, emphasizing their trimeric nature and the composition of their peptide chains. Points are assigned for different types of alterations in specific domains of the proteins, with higher points indicating more significant potential impact. The text mentions the ClinGen Skeletal Variant Curation Expert Panel (VCEP) funded by NHGRI and encourages readers to volunteer. Overall, the text provides insights into the genetic mechanisms and potential clinical implications of alterations in the COL2A1 gene.

Keywords

COL2A1 gene

truncating alterations

missense alterations

in-frame indels

haploinsufficiency

dominant negative effect

COL1A1 protein

COL1A2 protein

trimeric nature

ClinGen Skeletal Variant Curation Expert Panel

Pamela Ajuyah Robertson (proberts@broadinstitute.org)