ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.314G>A (p.Arg105His)

gnomAD frequency: 0.00001  dbSNP: rs773149185
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773445 SCV000907139 uncertain significance Cardiomyopathy 2024-12-23 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 105 of the TPM1 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function. 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 2/251456 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.
Fulgent Genetics, Fulgent Genetics RCV002501001 SCV002813315 uncertain significance Hypertrophic cardiomyopathy 3; Dilated cardiomyopathy 1Y 2021-10-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002536651 SCV003275130 uncertain significance Hypertrophic cardiomyopathy 2023-04-12 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. 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. ClinVar contains an entry for this variant (Variation ID: 628782). This variant has not been reported in the literature in individuals affected with TPM1-related conditions. This variant is present in population databases (rs773149185, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 105 of the TPM1 protein (p.Arg105His).
All of Us Research Program, National Institutes of Health RCV002536651 SCV004815444 uncertain significance Hypertrophic cardiomyopathy 2023-05-15 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the troponin T binding domain 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 the 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. This variant is rare in the general population and has been identified in 2/246226 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.

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