ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.982G>A (p.Ala328Thr)

gnomAD frequency: 0.00004  dbSNP: rs374545987
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755904 SCV000883554 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing The p.Ala328Thr variant (rs374545987) has not been reported in the medical literature. It is listed in the Exome Aggregation Consortium (ExAC) browser with an overall frequency of 0.007% (identified in 8 out of 120,060 chromosomes). The alanine at codon 328 is highly conserved considering 11 species up to Chicken (Alamut software v2.8.1), and computational analyses suggest this variant has a significant effect on CDH23 protein structure/function (SIFT: damaging, PolyPhen2: probably damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Ala328Thr variant cannot be determined with certainty.
Illumina Laboratory Services, Illumina RCV001108342 SCV001265568 uncertain significance Usher syndrome type 1D 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001108343 SCV001265569 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000755904 SCV001413497 likely benign not provided 2024-01-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000755904 SCV001475764 uncertain significance not provided 2019-10-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV001108343 SCV001523230 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 2019-09-10 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV000755904 SCV001982876 uncertain significance not provided 2023-02-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002493374 SCV002784195 uncertain significance Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2021-07-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003396316 SCV004104419 uncertain significance CDH23-related condition 2022-10-03 criteria provided, single submitter clinical testing The CDH23 c.982G>A variant is predicted to result in the amino acid substitution p.Ala328Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.089% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-73376998-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003472273 SCV004210622 uncertain significance Pituitary adenoma 5, multiple types 2023-09-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275419 SCV001460569 uncertain significance Usher syndrome type 1 2020-04-11 no assertion criteria provided clinical testing

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