ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.7685T>C (p.Val2562Ala) (rs143631346)

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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 RCV000723496 SCV000112906 uncertain significance not provided 2018-08-31 criteria provided, single submitter clinical testing
GeneDx RCV000723496 SCV000590514 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL6A3 gene. The V2562A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V2562A variant is observed in 18/10276 (0.2%) alleles from individuals of African background, in the ExAc dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V2562A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000306466 SCV000428740 likely benign Collagen VI-related myopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000813495 SCV000953857 uncertain significance Bethlem myopathy 1 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 2562 of the COL6A3 protein (p.Val2562Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs143631346, ExAC 0.2%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 94994). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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