Submissions for variant NM_001927.4(DES):c.449G>A (p.Arg150Gln)

dbSNP: rs876661344

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001368093	SCV001564471	uncertain significance	Desmin-related myofibrillar myopathy	2023-02-17	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 150 of the DES protein (p.Arg150Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 234985). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DES protein function.
AiLife Diagnostics, AiLife Diagnostics	RCV002223198	SCV002501153	uncertain significance	not provided	2022-01-19	criteria provided, single submitter	clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000223735	SCV000280072	uncertain significance	not specified	2015-03-20	no assertion criteria provided	clinical testing	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. Given a lack of case data (reviewed below) we consider this variant a variant of unknown significance. The variant has not been reported in the scientific literature or mutation databases. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. The Arg at codon 150 is conserved across species, as are neighboring amino acids. Other variants have not been reported in association with disease at this codon (150) and nearby codons (13-214 as of 3/23/2015 in Clinvar).In total the variant has not been seen in any laboratory controls, or published controls and individuals from publicly available population datasets. There is no variation at codon 150 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on 5200 Caucasian and African American individuals (as of March 23, 2015). There is no variation at codon 150 listed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of March 23, 2015). Of note: there were only 8,150 individuals who had sequencing with sufficient coverage to make calls on in that region of the DES gene.