ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.2321C>T (p.Thr774Ile)

gnomAD frequency: 0.00003  dbSNP: rs201755946
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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 RCV001886080 SCV002139902 uncertain significance Methylcobalamin deficiency type cblG 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 774 of the MTR protein (p.Thr774Ile). This variant is present in population databases (rs201755946, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1376705). 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: "Possibly 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 RCV002552210 SCV003545556 uncertain significance Inborn genetic diseases 2021-03-26 criteria provided, single submitter clinical testing The c.2321C>T (p.T774I) alteration is located in exon 22 (coding exon 22) of the MTR gene. This alteration results from a C to T substitution at nucleotide position 2321, causing the threonine (T) at amino acid position 774 to be replaced by an isoleucine (I). The in silico prediction for the p.T774I alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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