ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.8311G>A (p.Gly2771Ser) (rs201076440)

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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 RCV000154384 SCV000204050 uncertain significance not specified 2013-12-26 criteria provided, single submitter clinical testing The Gly2771Ser variant in CDH23 has been previously reported in the heterozygous state in one individual with Usher syndrome; however, a second variant in CDH23 was not identified (Oshima 2008). This variant has been identified in 0.06% (5/ 8412) of European American chromosomes by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS/; dbSNP rs201076440); however, this frequency is not high enough to rule out a pathogenic role. Computational analyses (biochemic al amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not p rovide strong support for or against an impact to the protein. In summary, addit ional data is needed to determine the clinical significance of this variant.
Invitae RCV001053772 SCV001218049 uncertain significance not provided 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2771 of the CDH23 protein (p.Gly2771Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs201076440, ExAC 0.08%), including at least one homozygous and/or hemizygous individual. This variant has been observed in an individual affected with Usher syndrome. However, in that individual a second variant was not identified (PMID: 18429043). ClinVar contains an entry for this variant (Variation ID: 177767). 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 C0"). 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.
Illumina Clinical Services Laboratory,Illumina RCV001102961 SCV001259662 uncertain significance Usher syndrome type 1D 2017-04-28 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 RCV001102962 SCV001259663 uncertain significance Deafness, autosomal recessive 12 2017-04-28 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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