ClinVar Miner

Submissions for variant NM_001032283.3(TMPO):c.565+1084T>A

dbSNP: rs767247716
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001972162 SCV002207988 uncertain significance Loeys-Dietz syndrome 2 2024-11-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 222 of the TMPO protein (p.Ile222Asn). This variant is present in population databases (rs767247716, gnomAD 0.007%). 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: 1435226). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TMPO protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV004042900 SCV005020323 uncertain significance not specified 2024-01-29 criteria provided, single submitter clinical testing The p.I222N variant (also known as c.665T>A), located in coding exon 4 of the TMPO gene, results from a T to A substitution at nucleotide position 665. The isoleucine at codon 222 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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