ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.430C>T (p.His144Tyr)

gnomAD frequency: 0.00001  dbSNP: rs747296848
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001207797 SCV001379164 uncertain significance Transcobalamin II deficiency 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 144 of the TCN2 protein (p.His144Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs747296848, ExAC 0.003%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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