ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs751433380
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Total submissions: 3
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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 Syndromic X-linked intellectual disability Hedera type 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 199 of the ATP6AP2 protein (p.Arg199His). This variant is present in population databases (rs751433380, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ATP6AP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 204918). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP6AP2 protein function. 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.
Ambry Genetics RCV002513980 SCV003543188 uncertain significance Inborn genetic diseases 2022-05-18 criteria provided, single submitter clinical testing The c.596G>A (p.R199H) alteration is located in exon 7 (coding exon 7) of the ATP6AP2 gene. This alteration results from a G to A substitution at nucleotide position 596, causing the arginine (R) at amino acid position 199 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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