ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5131G>A (p.Val1711Ile) (rs181611778)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001004784 SCV001164269 likely benign Usher syndrome 2019-10-29 reviewed by expert panel curation The c.5131 (p.Val1711Ile) variant has been identified in 0.3% (51/19534 CI 95%) of East Asian alleles in gnomAD (BS1). This variant was observed in 1 patient with Usher syndrome, without a second variant in CDH23 (PMID: 25333064). Computational prediction analysis using the metapredictor tool REVEL produced a score of .17; this combined with the presence of the isoleucine amino acid at position 1711 in 5 organisms including 3 mammals in UCSC suggests that the variant may not impact the protein (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1, BP4.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000479783 SCV000230527 uncertain significance not provided 2014-07-11 criteria provided, single submitter clinical testing
GeneDx RCV000479783 SCV000564846 likely pathogenic not provided 2013-04-08 criteria provided, single submitter clinical testing The V1711I missense change in the CDH23 gene has been reported as a variant with uncertain pathogenicity (Wagatsuma, 2007). The V1711I missense change was identified in one patient who did not harbor a second mutation as was absent from 292 control alleles (Wagatsuma, 2007). The V1711I amino acid substitution is conservative as both Valine and Isoleucine are neutral and non-polar residues. The residue at which this substitution occurs is well conserved within the cadherin 23 protein. According to the Human Gene Mutation Database (HGMD) another missense mutation at a nearby codon (Q1716P) has been reported in association with Usher syndrome. The V1711I variant was not observed at any significant frequency in approximately 6,300 individuals of European and African American ancestry in an external variant database. Therefore, V1711I is a strong candidate for a pathogenic variant, although the possibility that it is a benign polymorphism cannot be excluded.
Invitae RCV000479783 SCV001082996 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001104308 SCV001261161 uncertain significance Usher syndrome type 1D 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001107060 SCV001264189 uncertain significance Deafness, autosomal recessive 12 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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