ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.8729T>C (p.Met2910Thr)

gnomAD frequency: 0.00009  dbSNP: rs374171450
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520879 SCV000621693 uncertain significance not provided 2017-10-25 criteria provided, single submitter clinical testing The M2910T variant in the CDH23 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M2910T variant is observed in 10/34,410 (0.03%) alleles from individuals of Latino background in large population cohorts, and no individuals were reported to be homozygous (Lek et al., 2016). The M2910T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret M2910T as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000520879 SCV001393006 uncertain significance not provided 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2910 of the CDH23 protein (p.Met2910Thr). This variant is present in population databases (rs374171450, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 452849). 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 not expected to disrupt CDH23 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 RCV004609423 SCV005107700 uncertain significance Inborn genetic diseases 2024-06-10 criteria provided, single submitter clinical testing The c.8729T>C (p.M2910T) alteration is located in exon 61 (coding exon 60) of the CDH23 gene. This alteration results from a T to C substitution at nucleotide position 8729, causing the methionine (M) at amino acid position 2910 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001276059 SCV001461887 uncertain significance Usher syndrome type 1 2020-04-17 no assertion criteria provided clinical testing

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