ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5945A>G (p.Asn1982Ser)

gnomAD frequency: 0.00001  dbSNP: rs555432123
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483578 SCV000571379 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing The N1982S variant in the CDH23 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N1982S variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N1982S 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 N1982S as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000764920 SCV000896083 uncertain significance Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000483578 SCV001421834 uncertain significance not provided 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1982 of the CDH23 protein (p.Asn1982Ser). This variant is present in population databases (rs555432123, gnomAD 0.03%). This missense change has been observed in individual(s) with hearing loss (PMID: 31152317). ClinVar contains an entry for this variant (Variation ID: 422021). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Natera, Inc. RCV001274896 SCV001459449 uncertain significance Usher syndrome type 1 2020-09-16 no assertion criteria provided clinical testing

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