Submissions for variant NM_001849.4(COL6A2):c.1489C>A (p.Pro497Thr)

gnomAD frequency: 0.00013  dbSNP: rs75581470

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000329762	SCV000337217	likely benign	not specified	2015-11-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000270832	SCV000436691	likely benign	Myosclerosis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000325923	SCV000436692	benign	Collagen 6-related myopathy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000766751	SCV000583231	uncertain significance	not provided	2018-07-18	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the COL6A2 gene. The P497T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P497T variant is observed in 41/8600 (0.5%) alleles from individuals of East Asian background, in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P497T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087788	SCV000657109	likely benign	Bethlem myopathy 1A	2024-12-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004543048	SCV004772279	likely benign	COL6A2-related disorder	2020-09-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).