Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000304993 | SCV000458438 | 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. |
Invitae | RCV000642243 | SCV000763902 | likely benign | Methylcobalamin deficiency type cblE | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001591019 | SCV001824422 | uncertain significance | not provided | 2021-06-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge, in association with a MTRR-related disorder; This variant is associated with the following publications: (PMID: 31063268, 27535533) |
Ambry Genetics | RCV002520386 | SCV003743132 | uncertain significance | Inborn genetic diseases | 2020-12-11 | criteria provided, single submitter | clinical testing | The c.869T>C (p.I290T) alteration is located in exon 6 (coding exon 5) of the MTRR gene. This alteration results from a T to C substitution at nucleotide position 869, causing the isoleucine (I) at amino acid position 290 to be replaced by a threonine (T). The p.I290T alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
ARUP Laboratories, |
RCV001591019 | SCV003800185 | uncertain significance | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | The MTRR c.869T>C; p.Ile290Thr variant (rs144899305), to our knowledge, is not reported in an individual with homocystinuria-megaloblastic anemia, but is reported in the literature in an individual with cleft lip (Marini 2019). This variant is reported in ClinVar (Variation ID: 354357) and is found in the non-Finnish European population with an allele frequency of 0.18% (233/129,162 alleles) in the Genome Aggregation Database. The isoleucine at codon 290 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.148). Due to limited information, the clinical significance of the p.Ile290Thr variant is uncertain at this time. References: Marini NJ et al. Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate. Am J Med Genet A. 2019 Jul;179(7):1260-1269. PMID: 31063268. |
Baylor Genetics | RCV000642243 | SCV003836328 | uncertain significance | Methylcobalamin deficiency type cblE | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000642243 | SCV001459125 | likely benign | Methylcobalamin deficiency type cblE | 2020-05-01 | no assertion criteria provided | clinical testing |