ClinVar Miner

Submissions for variant NM_005765.3(ATP6AP2):c.596G>A (p.Arg199His) (rs751433380)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186821 SCV000240392 uncertain significance not provided 2013-12-01 criteria provided, single submitter clinical testing p.Arg199His (CGT>CAT): c.596 G>A in exon 7 of the ATP6AP2 gene (NM_005765.2). The Arg199His missense change in the ATP6AP2 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 5,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one positively charged amino acid for another at a position that is not highly conserved across species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Arg199His is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000541972 SCV000640010 uncertain significance Mental retardation, X-linked, syndromic, Hedera type 2017-06-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 199 of the ATP6AP2 protein (p.Arg199His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs751433380, ExAC 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with a ATP6AP2-related disease. ClinVar contains an entry for this variant (Variation ID: 204918). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on ATP6AP2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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