ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.883G>A (p.Val295Ile)

gnomAD frequency: 0.00009  dbSNP: rs770684965
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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 RCV001048562 SCV001212575 uncertain significance Transcobalamin II deficiency 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 295 of the TCN2 protein (p.Val295Ile). This variant is present in population databases (rs770684965, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 845491). 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 isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV004031516 SCV004963631 uncertain significance Inborn genetic diseases 2023-12-18 criteria provided, single submitter clinical testing The c.883G>A (p.V295I) alteration is located in exon 6 (coding exon 6) of the TCN2 gene. This alteration results from a G to A substitution at nucleotide position 883, causing the valine (V) at amino acid position 295 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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