Submissions for variant NM_004369.3(COL6A3):c.1975C>T (p.Arg659Cys) (rs146291186)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000725122	SCV000334257	uncertain significance	not provided	2018-07-24	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000319603	SCV000428852	likely benign	Collagen VI-related myopathy	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000725122	SCV000617950	uncertain significance	not provided	2018-12-27	criteria provided, single submitter	clinical testing	The R659C variant in the COL6A3 gene has not been reported previously as a pathogenic variant,nor as a benign variant, to our knowledge. The R659C variant was not observed at any significantfrequency in approximately 6500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The R659C variant is a non-conservative amino acid substitution, which occurs within the VWFA 4domain and Nonhelical region at a position where amino acids with similar properties to Arginine aretolerated across species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. We interpret R659C as a variant of uncertain significance.