Total submissions: 3
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, |
RCV000642242 | SCV002077209 | uncertain significance | Methylcobalamin deficiency type cblE | 2019-11-11 | no assertion criteria provided | clinical testing |