ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.994T>C (p.Tyr332His)

dbSNP: rs794728067
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181147 SCV000233424 uncertain significance not provided 2018-06-28 criteria provided, single submitter clinical testing p.Tyr332His (TAT>CAT): c.994 T>C in exon 8 of the DSC2 gene (NM_024422.3). The Y332H variant in the DSC2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The Y332H variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The Y332H variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. A mutation in a nearby residue (T340A) have been reported in association with ARVC supporting the functional importance of this region of the protein. However, the Y332 residue is not well conserved across species and in silico analysis predicts Y332H is benign to the protein structure/function. With the clinical and molecular information available at this time, we cannot definitively determine if Y332H is a disease-causing mutation or a rare benign variant.The variant is found in ARVC panel(s).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798634 SCV002043578 uncertain significance Cardiomyopathy 2020-08-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002381585 SCV002694389 uncertain significance Cardiovascular phenotype 2021-10-29 criteria provided, single submitter clinical testing The p.Y332H variant (also known as c.994T>C), located in coding exon 8 of the DSC2 gene, results from a T to C substitution at nucleotide position 994. The tyrosine at codon 332 is replaced by histidine, 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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