ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.515T>C (p.Ile172Thr) (rs199476312)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000024575 SCV000927459 likely pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148916 SCV000190662 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research
GeneDx RCV000024575 SCV000209310 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TPM1 gene. The I172T variant was reported as novel in one patient with HCM and a family history of HCM as well as sudden cardiac death (Van Driest et al., 2003). However, this study cohort was screened only for thin filament variants. Subsequently, Van Driest et al. (2004) reported I172T in an individual with HCM who also harbored an MYBPC3 variant, presumably the same patient from the 2003 study due to cohort overlap. Additionally, one functional study suggests that this variant does not impact protein function (Gupte et al., 2015), whereas a more recent functional study suggests this variant may lead to a milder phenotype (Matyushenko et al., 2017). Nevertheless, the I172T variant is not observed in large population cohorts (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Leiden Muscular Dystrophy (TPM1) RCV000024575 SCV000045882 not provided not provided 2012-04-15 no assertion provided curation
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000148916 SCV000747974 uncertain significance Primary familial hypertrophic cardiomyopathy 2017-03-21 criteria provided, single submitter clinical testing

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