ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1201C>T (p.Leu401Phe)

dbSNP: rs151150267
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000539301 SCV000623226 uncertain significance Bloom syndrome 2024-04-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 401 of the BLM protein (p.Leu401Phe). This variant is present in population databases (rs151150267, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This missense change has been observed to co-occur in individuals with a different variant in BLM that has been determined to be pathogenic (Invitae), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 454067). 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 RCV002350163 SCV002650526 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-30 criteria provided, single submitter clinical testing The p.L401F variant (also known as c.1201C>T), located in coding exon 5 of the BLM gene, results from a C to T substitution at nucleotide position 1201. The leucine at codon 401 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. RCV000539301 SCV001460774 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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