ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1237G>A (p.Glu413Lys)

gnomAD frequency: 0.00006  dbSNP: rs887921909
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000530944 SCV000623231 uncertain significance Bloom syndrome 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 413 of the BLM protein (p.Glu413Lys). This variant is present in population databases (no rsID available, gnomAD 0.008%). 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: 454072). 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.
Baylor Genetics RCV000530944 SCV001481292 uncertain significance Bloom syndrome 2019-07-09 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002367759 SCV002663142 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The p.E413K variant (also known as c.1237G>A), located in coding exon 6 of the BLM gene, results from a G to A substitution at nucleotide position 1237. The glutamic acid at codon 413 is replaced by lysine, an amino acid with similar properties. This alteration was reported in a study testing individuals from the Colon Cancer Family Registry Cohort (Raskin L et al. Oncotarget, 2017 Nov;8:93450-93463). 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.
Natera, Inc. RCV000530944 SCV002090018 uncertain significance Bloom syndrome 2017-08-09 no assertion criteria provided clinical testing

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