Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000217198 | SCV000270095 | likely benign | not specified | 2015-03-16 | criteria provided, single submitter | clinical testing | p.Ala135Val variant in exon 1 of DES: This variant is not expected to have clini cal significance due to a lack of conservation across species, including mammals . Of note, 4 mammals (naked mole-rat, star-nosed mole, opossum, and Tasmanian de vil) have a valine (Val) at this position despite high nearby amino acid conserv ation. It has been identified in 0.2% (16/8402) of South Asian chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs54 6741834). |
| Eurofins Ntd Llc |
RCV000725598 | SCV000338039 | uncertain significance | not provided | 2018-05-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000725598 | SCV000618838 | uncertain significance | not provided | 2024-04-03 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; In vitro studies confirmed that DES-A135V does not affect desmin filament formation (PMID: 36497166); This variant is associated with the following publications: (PMID: 26807690, 36497166) |
| Labcorp Genetics |
RCV001079455 | SCV000773406 | likely benign | Desmin-related myofibrillar myopathy | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000725598 | SCV002049798 | uncertain significance | not provided | 2020-10-29 | criteria provided, single submitter | clinical testing | The DES c.404C>T; p.Ala135Val variant (rs546741834), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 227281). This variant is found in the South Asian population with an allele frequency of 0.2% (46/24592 alleles, including 0 homozygotes) in the Genome Aggregation Database. The alanine at codon 135 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.2). Due to limited information, the clinical significance of the p.Ala135Val variant is uncertain at this time. Gene Statement: Pathogenic germline variants in DES are predominantly inherited in an autosomal dominant manner, and are associated with myofibrillar myopathy 1/desminopathy (MIM: 601419). Rare observations associated with neurogenic scapuloperoneal syndrome, Kaeser type (MIM: 181400) and non-syndromic dilated cardiomyopathy 1I (MIM: 604765) have been reported. |
| Ambry Genetics | RCV002321829 | SCV002629250 | benign | Cardiovascular phenotype | 2024-02-12 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
| Revvity Omics, |
RCV000725598 | SCV003829061 | uncertain significance | not provided | 2023-09-13 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000725598 | SCV004225993 | uncertain significance | not provided | 2022-12-07 | criteria provided, single submitter | clinical testing | BP4 |