ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3129T>G (p.Asn1043Lys)

gnomAD frequency: 0.00004  dbSNP: rs727502992
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Total submissions: 3
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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 RCV000150549 SCV000197778 uncertain significance not specified 2014-01-07 criteria provided, single submitter clinical testing The Asn1043Lys variant in DSG2 has not been reported in individuals with cardiom yopathy or in large population studies. Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that th is variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Additional information is needed to fully ass ess the clinical significance of the Asn1043Lys variant.
Invitae RCV001850045 SCV002196304 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1043 of the DSG2 protein (p.Asn1043Lys). This variant is present in population databases (rs727502992, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 163224). 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 DSG2 protein function with a negative predictive value of 95%. 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 RCV003162610 SCV003859070 uncertain significance Cardiovascular phenotype 2022-11-04 criteria provided, single submitter clinical testing The p.N1043K variant (also known as c.3129T>G), located in coding exon 15 of the DSG2 gene, results from a T to G substitution at nucleotide position 3129. The asparagine at codon 1043 is replaced by lysine, an amino acid with 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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