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

gnomAD frequency: 0.00073  dbSNP: rs144777709

Total submissions: 5

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.
Invitae	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	criteria provided, single submitter	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).