ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3770C>T (p.Pro1257Leu)

gnomAD frequency: 0.00002  dbSNP: rs372134818
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001021096 SCV001182671 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-31 criteria provided, single submitter clinical testing The p.P1257L variant (also known as c.3770C>T), located in coding exon 19 of the BLM gene, results from a C to T substitution at nucleotide position 3770. The proline at codon 1257 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001827202 SCV003485476 uncertain significance Bloom syndrome 2024-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1257 of the BLM protein (p.Pro1257Leu). This variant is present in population databases (rs372134818, gnomAD 0.04%). 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: 824188). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Natera, Inc. RCV001827202 SCV002090609 uncertain significance Bloom syndrome 2021-05-09 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.