ClinVar Miner

Submissions for variant NM_001848.2(COL6A1):c.2614C>T (p.Arg872Trp) (rs368561027)

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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 RCV000723506 SCV000111682 uncertain significance not provided 2012-08-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764265 SCV000895278 uncertain significance Bethlem myopathy 1; Ullrich congenital muscular dystrophy 1 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000723506 SCV000617764 uncertain significance not provided 2017-11-02 criteria provided, single submitter clinical testing The R872W variant in the COL6A1 gene has been reported previously in a patient with Down syndrome and an atrioventricular septal defect; however, additional clinical and family segregation information were not provided (Ackerman et al., 2012). The R872W variant is observed in 19/23246 (0.082%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The R872W 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R872W as a variant of uncertain significance.
Invitae RCV000653571 SCV000775452 uncertain significance Bethlem myopathy 1 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 872 of the COL6A1 protein (p.Arg872Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs368561027, ExAC 0.06%). This variant has not been reported in the literature in individuals with COL6A1-related disease. ClinVar contains an entry for this variant (Variation ID: 93862). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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