ClinVar Miner

Submissions for variant NM_001127453.2(GSDME):c.656A>G (p.Tyr219Cys)

dbSNP: rs1554325967
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000599863 SCV000712001 likely benign not specified 2016-05-02 criteria provided, single submitter clinical testing p.Tyr219Cys in exon 5 of DFNA5: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, 5 mammals have a cysteine (Cys) at this position despite high nearby amino acid conservation.
Labcorp Genetics (formerly Invitae), Labcorp RCV005091589 SCV005809172 uncertain significance not provided 2024-09-18 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 219 of the DFNA5 protein (p.Tyr219Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DFNA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 504951). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DFNA5 protein function with a negative predictive value of 80%. 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.

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