ClinVar Miner

Submissions for variant NM_005765.3(ATP6AP2):c.315T>G (p.Ser105Arg) (rs745748841)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186820 SCV000240391 uncertain significance not provided 2014-09-18 criteria provided, single submitter clinical testing p.Ser105Arg (AGT>AGG): c.315 T>G in exon 4 of the ATP6AP2 gene (NM_005765.2). A variant of unknown significance has been identified in the ATP6AP2 gene. The S105R variant 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 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S105R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved through mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in INFANT-EPI panel(s).
Invitae RCV000694376 SCV000822819 uncertain significance Mental retardation, X-linked, syndromic, Hedera type 2018-11-14 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 105 of the ATP6AP2 protein (p.Ser105Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs745748841, ExAC 0.004%). This variant has not been reported in the literature in individuals with ATP6AP2-related disease. ClinVar contains an entry for this variant (Variation ID: 204917). 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: "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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