Submissions for variant NM_001849.4(COL6A2):c.2935G>A (p.Asp979Asn)

gnomAD frequency: 0.00012  dbSNP: rs141579198

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000353251	SCV000333053	uncertain significance	not provided	2016-09-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000653559	SCV000775440	likely benign	Bethlem myopathy 1A	2024-12-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001141921	SCV001302305	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.
GeneDx	RCV000353251	SCV003805433	uncertain significance	not provided	2023-02-16	criteria provided, single submitter	clinical testing	Seen in an individual with limb-girdle muscular dystrophy in published literature (Nallamilli et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: Junkerov_2018, 30564623)
Revvity Omics, Revvity	RCV000353251	SCV003832510	uncertain significance	not provided	2022-01-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000353251	SCV005330291	uncertain significance	not provided	2024-08-01	criteria provided, single submitter	clinical testing	COL6A2: PM2
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000353251	SCV001550630	uncertain significance	not provided		no assertion criteria provided	clinical testing	The COL6A2 p.Asp979Asn variant was not identified in the literature but was identified in dbSNP (ID: rs141579198) and ClinVar (classified as uncertain significance by Invitae and EGL Genetics). The variant was identified in control databases in 51 of 275508 chromosomes at a frequency of 0.0001851 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 41 of 124892 chromosomes (freq: 0.000328), European (Finnish) in 4 of 22908 chromosomes (freq: 0.000175), Latino in 5 of 35300 chromosomes (freq: 0.000142) and Other in 1 of 7124 chromosomes (freq: 0.00014), but was not observed in the African, Ashkenazi Jewish, East Asian, or South Asian populations. The p.Asp979 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.