ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1235C>T (p.Thr412Met)

gnomAD frequency: 0.00002  dbSNP: rs775209685
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462668 SCV000543362 uncertain significance Bloom syndrome 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 412 of the BLM protein (p.Thr412Met). This variant is present in population databases (rs775209685, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 405299). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. 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 RCV001010480 SCV001170684 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-01 criteria provided, single submitter clinical testing The p.T412M variant (also known as c.1235C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1235. The threonine at codon 412 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477940 SCV004222425 uncertain significance not provided 2023-06-29 criteria provided, single submitter clinical testing This variant has not been reported in the germline of an individual affected with a BLM related disease in the published literature. The frequency of this variant in the general population, 0.000087 (3/34406 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000462668 SCV001461098 uncertain significance Bloom syndrome 2018-06-25 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.