ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.1141G>A (p.Ala381Thr)

gnomAD frequency: 0.00073  dbSNP: rs144777709
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000326202 SCV000356030 uncertain significance Disorders of Intracellular Cobalamin Metabolism 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000426813 SCV000535771 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing The A381T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A381T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, 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 RCV001463144 SCV001667079 likely benign Methylcobalamin deficiency type cblG 2024-01-29 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001463144 SCV004236650 uncertain significance Methylcobalamin deficiency type cblG 2023-06-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003957551 SCV004783414 likely benign MTR-related disorder 2022-07-12 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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