Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156602 | SCV000206321 | uncertain significance | not specified | 2014-08-19 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Leu466Ile varia nt in SLC17A8 has not been reported in individuals with hearing loss, but has be en identified in 1/1323 of European Chromosomes by the ClinSeq project (http://w ww.genome.gov/20519355; dbSNP rs201180712). The leucine (Leu) at position 466 is conserved in mammals, but not in birds or evolutionarily distant species, with scarlet macaw and softshell turtle having an isoleucine (Ile) at this position, supporting that this change may be tolerated. Additional computational predicti on tools also suggest this variant may not impact the protein, though this infor mation is not predictive enough to rule out pathogenicity. In summary, the clini cal significance of this variant cannot be determined with certainty; however, t he conservation and computational data suggest that it is more likely to be beni gn. |
| Gene |
RCV000767164 | SCV000536155 | uncertain significance | not provided | 2022-10-18 | 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 |
| Illumina Laboratory Services, |
RCV001113389 | SCV001271158 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 25 | 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. |
| Invitae | RCV000767164 | SCV002390344 | likely benign | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002515030 | SCV003736087 | uncertain significance | Inborn genetic diseases | 2022-12-21 | criteria provided, single submitter | clinical testing | The c.1396C>A (p.L466I) alteration is located in exon 11 (coding exon 11) of the SLC17A8 gene. This alteration results from a C to A substitution at nucleotide position 1396, causing the leucine (L) at amino acid position 466 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |