ClinVar Miner

Submissions for variant NM_012463.4(ATP6V0A2):c.1096C>T (p.Pro366Ser) (rs372416067)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000380335 SCV000376927 uncertain significance Cutis laxa with osteodystrophy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000522764 SCV000622040 uncertain significance not provided 2017-11-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ATP6V0A2 gene. The P366S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 9/126692 (0.01%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The P366S 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. This substitution occurs at a position that is conserved across species across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with cutis laxa (Stenson et al., 2014).
Invitae RCV001057370 SCV001221857 uncertain significance ALG9 congenital disorder of glycosylation 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 366 of the ATP6V0A2 protein (p.Pro366Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs372416067, ExAC 0.006%). This variant has not been reported in the literature in individuals with ATP6V0A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 307586). 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: 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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