ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.447C>A (p.His149Gln)

dbSNP: rs770630089
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001294358 SCV001483232 uncertain significance Transcobalamin II deficiency 2020-08-10 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 149 of the TCN2 protein (p.His149Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is present in population databases (rs770630089, ExAC 0.002%). This variant has not been reported in the literature in individuals with TCN2-related conditions. 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 glutamine 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. 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.

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