ClinVar Miner

Submissions for variant NM_001927.4(DES):c.1079C>T (p.Ala360Val)

gnomAD frequency: 0.00001  dbSNP: rs141592925
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001314645 SCV001505183 uncertain significance Desmin-related myofibrillar myopathy 2023-09-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 360 of the DES protein (p.Ala360Val). This variant is present in population databases (rs141592925, gnomAD 0.0009%). 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: 1015740). 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. 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.
Ambry Genetics RCV002418949 SCV002725033 uncertain significance Cardiovascular phenotype 2020-08-04 criteria provided, single submitter clinical testing The p.A360V variant (also known as c.1079C>T), located in coding exon 6 of the DES gene, results from a C to T substitution at nucleotide position 1079. The alanine at codon 360 is replaced by valine, an amino acid with similar properties. Different variants affecting this codon (p.A360P, c.1078G>C and p.A360S, c.1078G>T) have been reported in association with skeletal myopathy and/or cardiomyopathy (Goldfarb LG et al. Nat. Genet., 1998 Aug;19:402-3; Miszalski-Jamka K et al. Circ Cardiovasc Genet, 2017 Aug;10:). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002486230 SCV002784677 uncertain significance Dilated cardiomyopathy 1I; Desmin-related myofibrillar myopathy; Neurogenic scapuloperoneal syndrome, Kaeser type 2021-10-26 criteria provided, single submitter clinical testing
GeneDx RCV003166796 SCV003915035 uncertain significance not provided 2023-04-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Mayo Clinic Laboratories, Mayo Clinic RCV003166796 SCV004225995 uncertain significance not provided 2022-10-19 criteria provided, single submitter clinical testing

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