Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000197313 | SCV000252560 | uncertain significance | not provided | 2016-07-21 | criteria provided, single submitter | clinical testing | The R818H variant in the WFS1 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. However, a missense mutation at the same residue (R818C) has been reported in association with Wolfram syndrome. The R818H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R818H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across mammalian species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R818H as a variant of unknown significance. |
| Illumina Laboratory Services, |
RCV000300930 | SCV000450689 | uncertain significance | WFS1-Related Spectrum Disorders | 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. |
| Illumina Laboratory Services, |
RCV000339404 | SCV000450690 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 6 | 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. |
| Labcorp Genetics |
RCV000197313 | SCV002446849 | likely benign | not provided | 2024-12-23 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics, |
RCV003147402 | SCV003804305 | likely risk allele | Wolfram syndrome 1 | criteria provided, single submitter | research | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs575851859 in Wolfram's syndrome yet. |