ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4021G>A (p.Asp1341Asn) (rs121908351)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436619 SCV000521016 likely pathogenic not provided 2016-05-31 criteria provided, single submitter clinical testing The D1341N variant in the CDH23 gene has been published previously in association with Usher syndrome and hearing loss (de Brouwer et al., 2003; Pennings et al., 2004; Bujakowska et al., 2014), and was observed in trans with other pathogenic variants in these patients. The 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. D1341N is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic.
Invitae RCV000436619 SCV001587038 pathogenic not provided 2020-02-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1341 of the CDH23 protein (p.Asp1341Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs121908351, ExAC 0.002%). This variant has been observed in individual(s) with autosomal recessive non-syndromic hearing loss and with Usher syndrome (PMID: 12522556, 19683999). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4923). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Not Available; Align-GVGD: Class C1). For these reasons, this variant has been classified as Pathogenic. 5
OMIM RCV000005205 SCV000025382 pathogenic Deafness, autosomal recessive 12 2003-02-01 no assertion criteria provided literature only
Natera, Inc. RCV001272891 SCV001455315 likely pathogenic Usher syndrome type 1 2020-09-16 no assertion criteria provided clinical testing

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