Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000367761 | SCV000468423 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 5 | 2018-01-12 | 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. |
| ARUP Laboratories, |
RCV000367761 | SCV001471972 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 5 | 2019-09-11 | criteria provided, single submitter | clinical testing | The DFNA5 c.325G>A; p.Val109Ile variant (rs202227661), to our knowledge, is not reported in the medical literature but is reported as uncertain in ClinVar (Variation ID: 359857). This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.01 percent (identified on 41 out of 282,778 chromosomes). The valine at position 109 is highly conserved and computational analyses of the effects of the p.Val109Ile variant on protein structure and function is conflicting (SIFT: tolerated, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Val109Ile variant with certainty. |
| Gene |
RCV002286731 | SCV002576821 | uncertain significance | not provided | 2022-03-29 | 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 |
| Invitae | RCV002286731 | SCV003473631 | likely benign | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing |