ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.175G>C (p.Gly59Arg)

dbSNP: rs1555937077
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000516335 SCV000613478 likely pathogenic not provided 2018-12-27 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/199642 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Moderate co-segregation with disease in multiple families, but using affected individuals only.
Labcorp Genetics (formerly Invitae), Labcorp RCV000654839 SCV000776741 uncertain significance Charcot-Marie-Tooth Neuropathy X 2023-09-12 criteria provided, single submitter clinical testing This variant disrupts the p.Gly59 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 10093067), which suggests that this may be a clinically significant amino acid residue. 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. 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 GJB1 protein function. ClinVar contains an entry for this variant (Variation ID: 447427). This missense change has been observed in individual(s) with Charcot-Marie Tooth disease, type X (PMID: 10894999). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 59 of the GJB1 protein (p.Gly59Arg).
Inherited Neuropathy Consortium RCV000789852 SCV000929237 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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