ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.2305G>A (p.Ala769Thr) (rs142719863)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727373 SCV000196810 uncertain significance not provided 2016-07-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL6A3 gene. The A769T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, nor was it observed with any significant frequency in the 1000 Genomes Project. The A769T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico predicts this variant likely does not alter 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 RCV000371027 SCV000428841 likely benign Collagen VI-related myopathy 2016-06-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727373 SCV000707968 uncertain significance not provided 2017-04-26 criteria provided, single submitter clinical testing
Invitae RCV000804572 SCV000944488 uncertain significance Bethlem myopathy 1 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 769 of the COL6A3 protein (p.Ala769Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs142719863, ExAC 0.1%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 162554). 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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