ClinVar Miner

Submissions for variant NM_002454.3(MTRR):c.908C>T (p.Thr303Ile)

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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 RCV002588573 SCV003495975 uncertain significance Methylcobalamin deficiency type cblE 2022-08-19 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 303 of the MTRR protein (p.Thr303Ile). This variant is present in population databases (rs781093877, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MTRR-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 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 RCV002595443 SCV003749918 uncertain significance Inborn genetic diseases 2020-11-19 criteria provided, single submitter clinical testing The c.908C>T (p.T303I) alteration is located in exon 7 (coding exon 6) of the MTRR gene. This alteration results from a C to T substitution at nucleotide position 908, causing the threonine (T) at amino acid position 303 to be replaced by an isoleucine (I). The p.T303I alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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