ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.901C>G (p.Pro301Ala)

gnomAD frequency: 0.00006  dbSNP: rs766371534
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523352 SCV000620904 uncertain significance not provided 2017-09-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MTR gene. The P301A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P301A variant is observed in 7/66738 (0.01%) alleles from individuals of non-Finnish Eropean background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P301A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001858021 SCV002264765 uncertain significance Methylcobalamin deficiency type cblG 2022-03-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 301 of the MTR protein (p.Pro301Ala). This variant is present in population databases (rs766371534, gnomAD 0.009%). 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: 452126). 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: "Probably 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.

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