Submissions for variant NM_001018005.2(TPM1):c.164A>G (p.Asp55Gly)

dbSNP: rs1566937759

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000706303	SCV000835344	uncertain significance	Hypertrophic cardiomyopathy	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 55 of the TPM1 protein (p.Asp55Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TPM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 582268). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170565	SCV001333151	uncertain significance	Cardiomyopathy	2019-02-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001170565	SCV001355203	uncertain significance	Cardiomyopathy	2023-12-05	criteria provided, single submitter	clinical testing	Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the actin binding region of the TPM1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
Ambry Genetics	RCV003303195	SCV004003146	uncertain significance	Cardiovascular phenotype	2023-04-03	criteria provided, single submitter	clinical testing	The p.D55G variant (also known as c.164A>G), located in coding exon 2 of the TPM1 gene, results from an A to G substitution at nucleotide position 164. The aspartic acid at codon 55 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.