Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000199802 | SCV000252490 | uncertain significance | not specified | 2016-05-24 | criteria provided, single submitter | clinical testing | The R587Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The NHLBI Exome Sequencing Project reports R587Q was observed in 4/8,600 alleles from individuals of European background. The R587Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Eurofins Ntd Llc |
RCV000726428 | SCV000344553 | uncertain significance | not provided | 2018-05-29 | criteria provided, single submitter | clinical testing | |
| Personalized Diabetes Medicine Program, |
RCV000445430 | SCV000537014 | likely benign | Monogenic diabetes | 2016-10-07 | criteria provided, single submitter | research | ACMG Criteria: BS2 (type2diabetesgenetics.org), BP4 |
| Laboratory for Molecular Medicine, |
RCV000199802 | SCV000711252 | benign | not specified | 2017-05-02 | criteria provided, single submitter | clinical testing | p.Arg587Gln in exon 8 of WFS1: This variant is not expected to have clinical sig nificance because of its frequency in the general population and the lack of con servation of the amino acid. It has been identified in 0.4% (37/10152) of Ashke nazi Jewish chromosomes Genome Aggregation Database (gnomAD, http://gnomad.broad institute.org; dbSNP rs71539657). The arginine (Arg) at position 587 is not cons erved across species with 1 mammal (bushbaby) and 10 fish species having a gluta mine (Gln). Additional computational prediction tools do not suggest an impact t o the protein. |
| ARUP Laboratories, |
RCV000726428 | SCV000884919 | uncertain significance | not provided | 2017-07-11 | criteria provided, single submitter | clinical testing | The p.Arg587Gln variant (rs71539657) has not been reported in the medical literature; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 215361). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in Ashkenazi Jewish populations of 0.36% (identified in 37 out of 10,152 chromosomes). The arginine at codon 587 is moderately conserved considering 13 species (Alamut software v2.9), and computational analyses suggest this variant does not have a significant effect on WFS1 protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism). However, based on the available information, the clinical significance of the p.Arg587Gln variant cannot be determined with certainty. |
| Labcorp Genetics |
RCV000726428 | SCV001013412 | likely benign | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001155846 | SCV001317311 | likely benign | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Illumina Laboratory Services, |
RCV001155847 | SCV001317312 | 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. |
| Ambry Genetics | RCV002517275 | SCV003727068 | likely benign | Inborn genetic diseases | 2021-03-31 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| New York Genome Center | RCV003227712 | SCV003925190 | uncertain significance | Wolfram syndrome 1; Type 2 diabetes mellitus | 2022-06-17 | criteria provided, single submitter | clinical testing |