ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.6230G>A (p.Gly2077Asp) (rs1553553646)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557822 SCV000657371 pathogenic Bethlem myopathy 1 2019-10-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 2077 of the COL6A3 protein (p.Gly2077Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in an individual affected with intermediate collagen VI myopathy (PMID: 24038877) and in the heterozygous state in an individual affected with autosomal dominant Bethlem myopathy (PMID: 24907562). This variant is located within the triple helix domain of the COL6A3 protein. Glycine residues within the triple helix region are crucial to maintain fibrillar collagens structure and stability (PMID: 7695699, 19344236). In the case of COL6A3, missense substitutions that affect glycine residues within the triplex helix domain have been reported in many patients affected with collagen VI myopathy (PMID: 24038877). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000598340 SCV000707095 pathogenic not provided 2017-03-27 criteria provided, single submitter clinical testing

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