ClinVar Miner

Submissions for variant NM_001927.4(DES):c.404C>T (p.Ala135Val) (rs546741834)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized 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,; dbSNP rs54 6741834).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725598 SCV000338039 uncertain significance not provided 2018-05-16 criteria provided, single submitter clinical testing
GeneDx RCV000725598 SCV000618838 uncertain significance not provided 2018-03-26 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DES gene. The A135V variant has not been published as pathogenic or been reported as benign to our knowledge. However, it has been observed in one individual referred for neuromuscular disorder genetic testing at GeneDx. This individual harbored additional variants and no cardiac evaluation or segregation studies were available. This variant is observed in 48/24674 (0.2%) alleles from individuals of South Asian ancestry in large population cohorts (Lek et al., 2016). The A135V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV001079455 SCV000773406 likely benign Myofibrillar myopathy 1; Muscular dystrophy, limb-girdle, type 2R 2020-11-20 criteria provided, single submitter clinical testing

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