Submissions for variant NM_024422.6(DSC2):c.431T>C (p.Met144Thr)

dbSNP: rs794728065

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181137	SCV000233414	uncertain significance	not provided	2012-12-18	criteria provided, single submitter	clinical testing	p.Met144Thr (ATG>ACG): c.431 T>C in exon 4 of the DSC2 gene (NM_024422.3)The Met144Thr variant in the DSC2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Met144Thr results in a non-conservative amino acid substitution of a nonpolar Methionine with a polar Threonine at a position that is not well conserved in other species. Only one nearby mutation (Gly150Ala) has been reported in association with ARVC (Christensen A et al., 2010). However, the Met144Thr variant is not present in the 1000 Genomes database (Kersey P et al., 2010) and the NHLBI ESP Exome Variant Server reports Met144Thr was not observed in approximately 6000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.With the clinical and molecular information available at this time, we cannot definitively determine if Met144Thr is a disease-causing mutation or a rare benign variant. This result cannot be interpreted for diagnosis or used for family member screening at this time. The variant is found in ARVC panel(s).