ClinVar Miner

Submissions for variant NM_000117.3(EMD):c.77T>C (p.Val26Ala)

dbSNP: rs727505029
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156455 SCV000206174 uncertain significance not specified 2014-03-24 criteria provided, single submitter clinical testing The Val26Ala variant in EMD has not been previously reported in individuals with cardiomyopathy or Emery-Dreifuss muscular dystrophy. Data from large population studies is insufficient to assess the frequency of this variant. Computational prediction tools and conservation analysis suggest that this variant may not imp act the protein, though this information is not predictive enough to rule out pa thogenicity. Additional information is needed to fully assess the clinical signi ficance of the Val26Ala variant.
Invitae RCV001049941 SCV001214021 uncertain significance X-linked Emery-Dreifuss muscular dystrophy 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 26 of the EMD protein (p.Val26Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 26899768). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 179659). 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 EMD protein function. 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 RCV002408699 SCV002669149 uncertain significance Cardiovascular phenotype 2022-07-25 criteria provided, single submitter clinical testing The p.V26A variant (also known as c.77T>C), located in coding exon 1 of the EMD gene, results from a T to C substitution at nucleotide position 77. The valine at codon 26 is replaced by alanine, an amino acid with similar properties. This alteration has been reported in individuals with dilated cardiomyopathy (DCM), including segregating in some families (Cuenca S et al. J Heart Lung Transplant, 2016 05;35:625-35). This amino acid position is well conserved in available vertebrate species. 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.
Natera, Inc. RCV001826851 SCV002084670 uncertain significance Emery-Dreifuss muscular dystrophy 2020-08-10 no assertion criteria provided clinical testing

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