Submissions for variant NM_000256.3(MYBPC3):c.3293G>T (p.Trp1098Leu)

dbSNP: rs397516013

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158224	SCV000208159	uncertain significance	not provided	2012-12-06	criteria provided, single submitter	clinical testing	This variant is denoted p.Trp1098Leu (TGG>TTG): c.3293 G>T in exon 30 of the MYBPC3 gene (NM_000256.3). The Trp1098Leu variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Trp1098Leu results in a conservative amino acid substitution of one non-polar residue for another at a position that is conserved across species. In silico analysis predicts Trp1098Leu is benign to the protein structure/function. However, missense mutations affecting nearby residues (Glu1096Lys, Thr1109Ile) have been reported in association with HCM, supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Trp1098Leu was not observed in approximately 6,000 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 Trp1098Leu is a disease-causing mutation or a rare benign variant. The variant is found in HCM panel(s).