Submissions for variant NM_001018005.2(TPM1):c.607A>G (p.Asn203Asp)

dbSNP: rs1555409523

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000629029	SCV000749939	uncertain significance	Hypertrophic cardiomyopathy	2017-09-20	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with TPM1-related disease. This sequence change replaces asparagine with aspartic acid at codon 203 of the TPM1 protein (p.Asn203Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702695	SCV001930371	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001702695	SCV001951909	likely pathogenic	not provided		no assertion criteria provided	clinical testing