ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.3598G>T (p.Val1200Phe) (rs779028054)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522488 SCV000620148 uncertain significance not provided 2017-08-17 criteria provided, single submitter clinical testing The V1200F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V1200F variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000688426 SCV000816036 uncertain significance Bethlem myopathy 1 2018-06-18 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 1200 of the COL6A3 protein (p.Val1200Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is present in population databases (rs779028054, ExAC 0.002%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 451448). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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