ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2611G>A (p.Asp871Asn) (rs387906610)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000591047 SCV000700937 pathogenic not provided 2017-03-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778644 SCV000914976 likely pathogenic Collagen VI-related myopathy 2018-10-25 criteria provided, single submitter clinical testing The COL6A2 c.2611G>A (p.Asp871Asn) missense variant has been reported three studies and is found in a total of three individuals with collagen type VI-related disorders, including one in a homozygous state and two in a compound heterozygous state (Gualandi et al., 2009; Zamurs et al., 2015; Fan et al. 2018). The homozygote and one compound heterozygote exhibited Bethlem myopathy and the second compound heterozygote exhibited Ullrich congenital muscular dystrophy. The p.Asp871Asn variant was absent from 100 control subjects and is reported at a frequency of 0.000013 in the Total population of the Genome Aggregation Database. Functional studies conducted using proband fibroblasts and mammalian cells indicated that the p.Asp871Asn variant severely reduced collagen VI synthesis, assembly, and secretion (Gualandi et al., 2009; Zamurs et al., 2015). Based on the evidence, the p.Asp871Asn variant is classified as likely pathogenic for collagen type VI-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001054018 SCV001218311 pathogenic Bethlem myopathy 1 2019-10-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 871 of the COL6A2 protein (p.Asp871Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs387906610, ExAC 0.04%). This variant has been observed in individual(s) with autosomal recessive Bethlem and Ullrich congenital muscular dystrophy (PMID: 19949035, 25533456, 29419890). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 29644). This variant has been reported to affect COL6A2 protein function (PMID: 19949035, 25533456). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000022492 SCV000043781 pathogenic BETHLEM MYOPATHY 1, AUTOSOMAL RECESSIVE 2009-12-01 no assertion criteria provided literature only

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