ClinVar Miner

Submissions for variant NM_138691.3(TMC1):c.928A>G (p.Thr310Ala)

gnomAD frequency: 0.00006  dbSNP: rs144501871
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001767608 SCV001998497 uncertain significance not provided 2020-09-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001767608 SCV002207547 uncertain significance not provided 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 310 of the TMC1 protein (p.Thr310Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs144501871, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with TMC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV004681242 SCV005180345 uncertain significance Inborn genetic diseases 2024-04-04 criteria provided, single submitter clinical testing The c.928A>G (p.T310A) alteration is located in exon 14 (coding exon 10) of the TMC1 gene. This alteration results from a A to G substitution at nucleotide position 928, causing the threonine (T) at amino acid position 310 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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