Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036835 | SCV000060490 | uncertain significance | not specified | 2012-12-28 | criteria provided, single submitter | clinical testing | The Arg146His variant in DFNB59 has not been reported in the literature nor prev iously identified by our laboratory. Computational analyses (biochemical amino a cid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the A rg146His variant may not impact the protein and several species (chicken and wes tern clawed frog) carry a histidine (His) as this position; however, this inform ation is not predictive enough to rule out pathogenicity. This variant has been identified in 0.01% (1/8306) of European American chromosomes in a broad populat ion by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/). A lthough this variant has been seen in the general population, its frequency is n ot high enough to rule out a pathogenic role. In summary, additional data is nee ded to determine the clinical significance of this variant. |
| Illumina Laboratory Services, |
RCV001133848 | SCV001293562 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 59 | 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. |