Submissions for variant NM_001927.4(DES):c.1027G>A (p.Asp343Asn)

gnomAD frequency: 0.00001  dbSNP: rs763903197

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726231	SCV000235787	uncertain significance	not provided	2022-06-10	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; This variant is associated with the following publications: (PMID: 26807690)
Eurofins Ntd Llc (ga)	RCV000726231	SCV000343093	uncertain significance	not provided	2017-01-30	criteria provided, single submitter	clinical testing
Invitae	RCV000651546	SCV000773400	uncertain significance	Desmin-related myofibrillar myopathy	2023-08-17	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 343 of the DES protein (p.Asp343Asn). 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. 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. ClinVar contains an entry for this variant (Variation ID: 201706). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is present in population databases (rs763903197, gnomAD 0.006%).
Fulgent Genetics, Fulgent Genetics	RCV002503715	SCV002812736	uncertain significance	Dilated cardiomyopathy 1I; Desmin-related myofibrillar myopathy; Neurogenic scapuloperoneal syndrome, Kaeser type	2021-08-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000726231	SCV003829047	uncertain significance	not provided	2019-05-24	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486739	SCV004240477	uncertain significance	Cardiomyopathy	2023-03-29	criteria provided, single submitter	clinical testing