ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.838G>A (p.Asp280Asn)

gnomAD frequency: 0.00001  dbSNP: rs777635889
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001327832 SCV001518922 uncertain significance Hypertrophic cardiomyopathy 2024-09-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 280 of the TPM1 protein (p.Asp280Asn). This variant is present in population databases (rs777635889, gnomAD 0.01%). 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: 1027266). 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 tolerated. 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 RCV001799067 SCV002042875 uncertain significance Cardiomyopathy 2020-03-03 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001799067 SCV004360791 uncertain significance Cardiomyopathy 2023-10-09 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 280 of the TPM1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 been identified in 4/282218 chromosomes 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.
All of Us Research Program, National Institutes of Health RCV001327832 SCV004818636 uncertain significance Hypertrophic cardiomyopathy 2023-03-28 criteria provided, single submitter clinical testing

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