ClinVar Miner

Submissions for variant NM_002454.3(MTRR):c.208C>T (p.Arg70Cys)

gnomAD frequency: 0.00005  dbSNP: rs374239028
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000322148 SCV000458421 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000811882 SCV000952172 uncertain significance Methylcobalamin deficiency type cblE 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 70 of the MTRR protein (p.Arg70Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs374239028, ExAC 0.05%). This variant has not been reported in the literature in individuals affected with MTRR-related conditions. ClinVar contains an entry for this variant (Variation ID: 354343). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV003168548 SCV003862757 uncertain significance Inborn genetic diseases 2023-02-15 criteria provided, single submitter clinical testing The c.208C>T (p.R70C) alteration is located in exon 3 (coding exon 2) of the MTRR gene. This alteration results from a C to T substitution at nucleotide position 208, causing the arginine (R) at amino acid position 70 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000811882 SCV001458139 uncertain significance Methylcobalamin deficiency type cblE 2020-09-16 no assertion criteria provided clinical testing

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