ClinVar Miner

Submissions for variant NM_012463.4(ATP6V0A2):c.1018C>T (p.Arg340Trp)

gnomAD frequency: 0.00003  dbSNP: rs781305219
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520087 SCV000620570 uncertain significance not provided 2017-09-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ATP6V0A2 gene. The R340W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R340W variant is observed in 7/16492 (0.04%) alleles from individuals of South Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server)]. The R340W 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. However, this substitution occurs at a position that is not conserved, and 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 variant or a rare benign variant.
Fulgent Genetics, Fulgent Genetics RCV000763804 SCV000894718 uncertain significance Cutis laxa with osteodystrophy; Wrinkly skin syndrome 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002527632 SCV003520452 uncertain significance ALG9 congenital disorder of glycosylation 2022-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 340 of the ATP6V0A2 protein (p.Arg340Trp). This variant is present in population databases (rs781305219, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with ATP6V0A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 451817). 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 ATP6V0A2 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 RCV004678730 SCV005174501 uncertain significance Inborn genetic diseases 2024-05-20 criteria provided, single submitter clinical testing The c.1018C>T (p.R340W) alteration is located in exon 9 (coding exon 9) of the ATP6V0A2 gene. This alteration results from a C to T substitution at nucleotide position 1018, causing the arginine (R) at amino acid position 340 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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