ClinVar Miner

Submissions for variant NM_000370.3(TTPA):c.175C>T (p.Arg59Trp)

gnomAD frequency: 0.00001  dbSNP: rs397515522
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000055793 SCV000800604 uncertain significance Familial isolated deficiency of vitamin E 2017-10-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002514279 SCV003440647 uncertain significance not provided 2022-03-26 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 59 of the TTPA protein (p.Arg59Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with ataxia with vitamin E deficiency (PMID: 9463307, 17049453). ClinVar contains an entry for this variant (Variation ID: 65589). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects TTPA function (PMID: 15065857, 23599266). 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.
Baylor Genetics RCV000055793 SCV004207496 pathogenic Familial isolated deficiency of vitamin E 2022-10-18 criteria provided, single submitter clinical testing
GeneReviews RCV000055793 SCV000086762 not provided Familial isolated deficiency of vitamin E no assertion provided literature only

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