Submissions for variant NM_000057.4(BLM):c.2872G>A (p.Val958Met)

gnomAD frequency: 0.00001  dbSNP: rs775006576

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000805418	SCV000945373	uncertain significance	Bloom syndrome	2023-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 958 of the BLM protein (p.Val958Met). This variant is present in population databases (rs775006576, gnomAD 0.006%). 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: 650294). 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 expected to disrupt BLM protein function with a positive 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	RCV001016865	SCV001177864	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-25	criteria provided, single submitter	clinical testing	The p.V958M variant (also known as c.2872G>A), located in coding exon 14 of the BLM gene, results from a G to A substitution at nucleotide position 2872. The valine at codon 958 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV000805418	SCV001781341	uncertain significance	Bloom syndrome	2021-07-14	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001724159	SCV001951526	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001724159	SCV001967825	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000805418	SCV002088131	uncertain significance	Bloom syndrome	2019-02-19	no assertion criteria provided	clinical testing