Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159365 | SCV000209311 | uncertain significance | not provided | 2017-03-29 | criteria provided, single submitter | clinical testing | The I172M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I172M variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the I172M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Invitae | RCV003765002 | SCV004636931 | uncertain significance | Hypertrophic cardiomyopathy | 2023-07-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 181665). 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. 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 isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 172 of the TPM1 protein (p.Ile172Met). |