Submissions for variant NM_001018005.2(TPM1):c.431A>G (p.Gln144Arg)

dbSNP: rs1566962338

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769480	SCV000900875	uncertain significance	Cardiomyopathy	2017-09-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001585694	SCV001812885	uncertain significance	not provided	2021-05-12	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV003748277	SCV004430135	uncertain significance	Hypertrophic cardiomyopathy	2023-02-06	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 626551). This variant has not been reported in the literature in individuals affected with TPM1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 144 of the TPM1 protein (p.Gln144Arg).
All of Us Research Program, National Institutes of Health	RCV003748277	SCV004830139	uncertain significance	Hypertrophic cardiomyopathy	2023-06-08	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 144 of the TPM1 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TPM1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.