ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1301A>G (p.Asn434Ser) (rs139287714)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150275 SCV000197293 uncertain significance not specified 2015-02-18 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Asn434Ser var iant in CDH23 has been previously identified by our laboratory in 1 individual w ith hearing loss who did not carry a second CDH23 variant. This variant has also been identified in 0.2% (24/9802) of African chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs139287714). Althoug h this variant has been seen in the general population, its frequency is not hig h enough to rule out a pathogenic role. Computational prediction tools and conse rvation analyses suggest that this variant may impact the protein, though this i nformation is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty; howev er, the frequency data suggest that it is more likely to be benign.
GeneDx RCV000731528 SCV000570876 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing The N434S variant in the CDH23 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports N434S was observed in 10/4076 alleles (0.24%) from individuals of African American background. The N434S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N434S as a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000731528 SCV000859359 uncertain significance not provided 2018-02-01 criteria provided, single submitter clinical testing
Invitae RCV000731528 SCV001059653 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing

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