ClinVar Miner

Submissions for variant NM_001927.4(DES):c.893C>T (p.Ser298Leu)

gnomAD frequency: 0.00014  dbSNP: rs62636491
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171830 SCV000055125 uncertain significance Primary dilated cardiomyopathy 2018-04-05 criteria provided, single submitter research
Eurofins NTD LLC (GA) RCV000056814 SCV000335234 uncertain significance not provided 2015-09-11 criteria provided, single submitter clinical testing
GeneDx RCV000056814 SCV000491114 uncertain significance not provided 2019-04-11 criteria provided, single submitter clinical testing Reported previously in a patient with DCM but no reported myopathy; however segregation data were not provided (Taylor et al., 2007); Functional studies show disruption of desmin filament assembly in the presence of the S298L variant (Taylor et al., 2007); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30564623, 23299917, 23861362, 17325244, 23143191, 22337857, 20474083, 27896284, 29926427)
Invitae RCV000466593 SCV000552184 uncertain significance Desmin-related myofibrillar myopathy 2021-12-15 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 298 of the DES protein (p.Ser298Leu). This variant is present in population databases (rs62636491, gnomAD 0.03%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 17325244, 23861362). ClinVar contains an entry for this variant (Variation ID: 66423). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Illumina Laboratory Services,Illumina RCV001142372 SCV001302806 uncertain significance Dilated cardiomyopathy 1I 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services,Illumina RCV000466593 SCV001302807 benign Desmin-related myofibrillar myopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services,Illumina RCV001143228 SCV001303735 benign Neurogenic scapuloperoneal syndrome, Kaeser type 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Athena Diagnostics Inc RCV000056814 SCV001475073 uncertain significance not provided 2020-03-18 criteria provided, single submitter clinical testing
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056814 SCV000087927 not provided not provided no assertion provided not provided
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000735983 SCV000864165 likely pathogenic Cardiomyopathy 2019-01-03 no assertion criteria provided clinical testing

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