ClinVar Miner

Submissions for variant NM_181703.4(GJA5):c.275A>C (p.Tyr92Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003260536 SCV003954173 uncertain significance Inborn genetic diseases 2023-05-17 criteria provided, single submitter clinical testing The c.275A>C (p.Y92S) alteration is located in exon 2 (coding exon 1) of the GJA5 gene. This alteration results from a A to C substitution at nucleotide position 275, causing the tyrosine (Y) at amino acid position 92 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003779908 SCV004568707 uncertain significance Atrial standstill 1; Atrial fibrillation, familial, 11 2024-06-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 92 of the GJA5 protein (p.Tyr92Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GJA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 2522496). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJA5 protein function with a positive 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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