ClinVar Miner

Submissions for variant NM_001032283.3(TMPO):c.565+1384A>G

gnomAD frequency: 0.00001  dbSNP: rs766401550
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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 RCV001312300 SCV001502747 uncertain significance Loeys-Dietz syndrome 2 2020-03-03 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TMPO-related conditions. This variant is present in population databases (rs766401550, ExAC 0.002%). This sequence change replaces tyrosine with cysteine at codon 322 of the TMPO protein (p.Tyr322Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine.
Ambry Genetics RCV004034251 SCV005020396 uncertain significance not specified 2023-10-19 criteria provided, single submitter clinical testing The p.Y322C variant (also known as c.965A>G), located in coding exon 4 of the TMPO gene, results from an A to G substitution at nucleotide position 965. The tyrosine at codon 322 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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