ClinVar Miner

Submissions for variant NM_001042517.2(DIAPH3):c.1291A>G (p.Thr431Ala)

gnomAD frequency: 0.00019  dbSNP: rs746390263
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375083 SCV001571900 uncertain significance Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PM2_Supporting, PP3_Supporting
GeneDx RCV001551493 SCV001772014 likely benign not provided 2019-12-09 criteria provided, single submitter clinical testing 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; Splice predictors are inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Labcorp Genetics (formerly Invitae), Labcorp RCV001551493 SCV002134484 uncertain significance not provided 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 431 of the DIAPH3 protein (p.Thr431Ala). This variant is present in population databases (rs746390263, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DIAPH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1064885). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV004037616 SCV003679414 uncertain significance not specified 2021-07-09 criteria provided, single submitter clinical testing The c.1291A>G (p.T431A) alteration is located in exon 12 (coding exon 12) of the DIAPH3 gene. This alteration results from a A to G substitution at nucleotide position 1291, causing the threonine (T) at amino acid position 431 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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