ClinVar Miner

Submissions for variant NM_001032283.3(TMPO):c.565+2247C>T

gnomAD frequency: 0.00003  dbSNP: rs369379490
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000692559 SCV000820387 uncertain significance Loeys-Dietz syndrome 2 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 610 of the TMPO protein (p.Arg610Cys). This variant is present in population databases (rs369379490, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. ClinVar contains an entry for this variant (Variation ID: 571419). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMPO protein function with a negative predictive value of 80%. 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.
GeneDx RCV001771958 SCV001992669 uncertain significance not provided 2019-02-08 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported as a variant of uncertain significance in ClinVar but additional evidence is not available (SCV000820387.1; Landrum et al., 2016)
Ambry Genetics RCV004025121 SCV002711128 likely benign not specified 2023-04-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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