ClinVar Miner

Submissions for variant NM_001927.4(DES):c.196C>A (p.Leu66Met)

gnomAD frequency: 0.00002  dbSNP: rs1320380570
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000651540 SCV000773394 uncertain significance Desmin-related myofibrillar myopathy 2023-11-15 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 66 of the DES protein (p.Leu66Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 541300). 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 not expected to disrupt DES protein function with a negative predictive value of 80%. 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 RCV002422410 SCV002721274 uncertain significance Cardiovascular phenotype 2021-10-13 criteria provided, single submitter clinical testing The p.L66M variant (also known as c.196C>A), located in coding exon 1 of the DES gene, results from a C to A substitution at nucleotide position 196. The leucine at codon 66 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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