Submissions for variant NM_001849.4(COL6A2):c.2197G>A (p.Gly733Arg)

gnomAD frequency: 0.00001  dbSNP: rs886042922

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000337022	SCV000337415	uncertain significance	not provided	2018-01-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001265687	SCV001443854	uncertain significance	Inborn genetic diseases	2019-01-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001303665	SCV001492916	pathogenic	Bethlem myopathy 1A	2023-09-26	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 733 of the COL6A2 protein (p.Gly733Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant COL6A2-related conditions (PMID: 30564623, 34167565). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 284693). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL6A2 protein function. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000337022	SCV001747335	uncertain significance	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000337022	SCV003832530	uncertain significance	not provided	2023-01-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000337022	SCV005376416	uncertain significance	not provided	2024-04-17	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33441455, 30564623, 34167565)
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477924	SCV000536776	uncertain significance	Bethlem myopathy 1A; Ullrich congenital muscular dystrophy 1A; Myosclerosis	2015-06-20	no assertion criteria provided	research
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000337022	SCV001809096	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000337022	SCV001956182	uncertain significance	not provided		no assertion criteria provided	clinical testing