Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150276 | SCV000197294 | uncertain significance | not specified | 2013-11-03 | criteria provided, single submitter | clinical testing | The Asp455Asn variant in CDH23 has not been reported in individuals with hearing loss or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide st rong support for or against an impact to the protein. In summary, additional dat a is needed to determine the clinical significance of this variant. |
Illumina Laboratory Services, |
RCV001108431 | SCV001265661 | 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. |
Illumina Laboratory Services, |
RCV001108432 | SCV001265662 | 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. |
Invitae | RCV001850038 | SCV002181379 | uncertain significance | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 455 of the CDH23 protein (p.Asp455Asn). This variant is present in population databases (rs727502920, gnomAD 0.004%). This missense change has been observed in individual(s) with sensorineural hearing loss (PMID: 26763877). ClinVar contains an entry for this variant (Variation ID: 162881). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDH23 protein function. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000150276 | SCV003844650 | uncertain significance | not specified | 2023-02-13 | criteria provided, single submitter | clinical testing | Variant summary: CDH23 c.1363G>A (p.Asp455Asn) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 249302 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1363G>A has been reported in the literature in an individual affected with sensorineural hearing loss (Sakuma_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV001271844 | SCV001453316 | uncertain significance | Usher syndrome type 1 | 2020-09-16 | no assertion criteria provided | clinical testing |