ClinVar Miner

Submissions for variant NM_001195248.2(APTX):c.740G>A (p.Arg247Gln)

gnomAD frequency: 0.00004  dbSNP: rs142133683
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001844149 SCV000479626 uncertain significance Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000372390 SCV000479627 uncertain significance Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 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.
CeGaT Center for Human Genetics Tuebingen RCV000999149 SCV001155626 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000999149 SCV001783432 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000999149 SCV002204433 uncertain significance not provided 2021-05-12 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 366591). This variant is present in population databases (rs142133683, ExAC 0.004%). This sequence change replaces arginine with glutamine at codon 247 of the APTX protein (p.Arg247Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine.

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