ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.2428G>A (p.Val810Met) (rs72653795)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489525 SCV000576956 uncertain significance not provided 2017-04-13 criteria provided, single submitter clinical testing The V810M variant in the ABCC6 gene has been reported previously in an adult male with pseudoxanthoma elasticum (PXE) who also harbored another missense variant (R1114C) in unknown phase with V810M (Gheduzzi et al., 2004). Although no homozygous individuals were reported, the V810M variant is observed in 2/8652 alleles (0.023%) from individuals of East Asian background in the ExAC dataset (Lek et al., 2016). The V810M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R807W, R807Q, and T811M) have been reported in the Human Gene Mutation Database in association with PXE (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the updated population data and review of the data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret V810M as a variant of uncertain significance.
PXE International RCV000499307 SCV000589011 pathogenic Pseudoxanthoma elasticum no assertion criteria provided research

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