ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1238A>T (p.Glu413Val)

gnomAD frequency: 0.00001  dbSNP: rs1215111361
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
Ambry Genetics RCV001010491 SCV001170698 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-17 criteria provided, single submitter clinical testing The p.E413V variant (also known as c.1238A>T), located in coding exon 6 of the BLM gene, results from an A to T substitution at nucleotide position 1238. The glutamic acid at codon 413 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001239381 SCV001412254 uncertain significance Bloom syndrome 2024-08-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 413 of the BLM protein (p.Glu413Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 818675). 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%. Studies have shown that this missense change is associated with inconclusive levels of altered splicing (internal data). 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.
Genetic Services Laboratory, University of Chicago RCV001819722 SCV002071795 uncertain significance not specified 2021-08-09 criteria provided, single submitter clinical testing DNA sequence analysis of the BLM gene demonstrated a sequence change, c.1238A>T, in exon 7 that results in an amino acid change, p.Glu413Val. This sequence change has been described in the gnomAD database in two heterozygous individuals which corresponds to a population frequency of 0.0008% (dbSNP rs1215111361). The p.Glu413Val change affects a poorly conserved amino acid residue located in a domain of the BLM protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Glu413Val substitution. This sequence change does not appear to have been previously described in individuals with BLM-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Glu413Val change remains unknown at this time.
Natera, Inc. RCV001239381 SCV002090019 uncertain significance Bloom syndrome 2020-03-31 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.