ClinVar Miner

Submissions for variant NM_001927.4(DES):c.1034T>C (p.Leu345Pro)

dbSNP: rs57639980
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000056765 SCV000841804 pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant appears to be associated with disease in at least one family. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant caused disruption of mitochondrial structures (PMID: 16217025).
Invitae RCV001044194 SCV001207976 pathogenic Desmin-related myofibrillar myopathy 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 345 of the DES protein (p.Leu345Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant myofibrillar myopathy (PMID: 10545598). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16825). 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) performed at Invitae indicates that this missense variant is expected to disrupt DES protein function. Experimental studies have shown that this missense change affects DES function (PMID: 10545598, 18563598). For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000056765 SCV001433465 pathogenic not provided 2020-01-03 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000056765 SCV002024039 likely pathogenic not provided 2022-04-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000056765 SCV004704299 pathogenic not provided 2024-01-01 criteria provided, single submitter clinical testing DES: PP1:Strong, PM1, PM2, PS3:Moderate, PS4:Moderate, PP3
OMIM RCV001044194 SCV000038598 pathogenic Desmin-related myofibrillar myopathy 1999-11-01 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056765 SCV000087878 not provided not provided no assertion provided not provided

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