ClinVar Miner

Submissions for variant NM_001927.4(DES):c.529G>A (p.Asp177Asn)

dbSNP: rs1057524813
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000435976 SCV000536525 uncertain significance not provided 2018-11-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DES gene. The D177N variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; ExAC). The D177N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to aspartic acid (D) are tolerated across species. Furthermore, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV001861644 SCV002292784 uncertain significance Desmin-related myofibrillar myopathy 2021-08-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 177 of the DES protein (p.Asp177Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 393156). This variant has not been reported in the literature in individuals affected with DES-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database.

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