Submissions for variant NM_004369.4(COL6A3):c.775G>A (p.Ala259Thr)

gnomAD frequency: 0.00074  dbSNP: rs141609058

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178213	SCV000230233	benign	not specified	2014-05-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000355357	SCV000428884	benign	Collagen 6-related myopathy	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088802	SCV001129748	likely benign	Bethlem myopathy 1A	2023-12-18	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000981752	SCV001143277	likely benign	not provided	2018-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000981752	SCV001811699	uncertain significance	not provided	2023-06-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002516770	SCV003725373	uncertain significance	Inborn genetic diseases	2022-11-17	criteria provided, single submitter	clinical testing	The c.775G>A (p.A259T) alteration is located in exon 4 (coding exon 3) of the COL6A3 gene. This alteration results from a G to A substitution at nucleotide position 775, causing the alanine (A) at amino acid position 259 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004553004	SCV004729093	likely benign	COL6A3-related disorder	2022-12-28	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).