ClinVar Miner

Submissions for variant NM_001927.4(DES):c.167T>A (p.Val56Glu)

gnomAD frequency: 0.00002  dbSNP: rs1170549656
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594634 SCV000706455 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001242921 SCV001416043 uncertain significance Desmin-related myofibrillar myopathy 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 56 of the DES protein (p.Val56Glu). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of DES-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 500483). Invitae Evidence 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 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001584405 SCV001821432 uncertain significance not specified 2021-08-30 criteria provided, single submitter clinical testing Variant summary: DES c.167T>A (p.Val56Glu) results in a non-conservative amino acid change located in the Intermediate filament head, DNA-binding domain (IPR006821) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 150664 control chromosomes (gnomAD v3.1 genomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.167T>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV000594634 SCV002578518 uncertain significance not provided 2022-04-06 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26807690)
Ambry Genetics RCV002404609 SCV002712830 uncertain significance Cardiovascular phenotype 2022-08-22 criteria provided, single submitter clinical testing The p.V56E variant (also known as c.167T>A), located in coding exon 1 of the DES gene, results from a T to A substitution at nucleotide position 167. The valine at codon 56 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002483625 SCV002785802 uncertain significance Dilated cardiomyopathy 1I; Desmin-related myofibrillar myopathy; Neurogenic scapuloperoneal syndrome, Kaeser type 2021-09-15 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000594634 SCV003829057 uncertain significance not provided 2019-04-18 criteria provided, single submitter clinical testing

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