ClinVar Miner

Submissions for variant NM_002454.3(MTRR):c.1246T>C (p.Phe416Leu)

gnomAD frequency: 0.00006  dbSNP: rs769915505
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000642242 SCV000763901 uncertain significance Methylcobalamin deficiency type cblE 2021-09-20 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 416 of the MTRR protein (p.Phe416Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs769915505, ExAC 0.01%). 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 leucine 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 RCV002544667 SCV003691276 uncertain significance Inborn genetic diseases 2021-11-08 criteria provided, single submitter clinical testing The c.1246T>C (p.F416L) alteration is located in exon 9 (coding exon 8) of the MTRR gene. This alteration results from a T to C substitution at nucleotide position 1246, causing the phenylalanine (F) at amino acid position 416 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000642242 SCV002077209 uncertain significance Methylcobalamin deficiency type cblE 2019-11-11 no assertion criteria provided clinical testing

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