ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.425T>C (p.Ile142Thr)

gnomAD frequency: 0.00001  dbSNP: rs200483369
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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 RCV001247755 SCV001421196 uncertain significance Transcobalamin II deficiency 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 142 of the TCN2 protein (p.Ile142Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs200483369, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV002568682 SCV003594273 uncertain significance Inborn genetic diseases 2021-12-04 criteria provided, single submitter clinical testing The c.425T>C (p.I142T) alteration is located in exon 3 (coding exon 3) of the TCN2 gene. This alteration results from a T to C substitution at nucleotide position 425, causing the isoleucine (I) at amino acid position 142 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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