ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3354C>A (p.Phe1118Leu)

dbSNP: rs1351493073
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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 RCV000628630 SCV000749534 uncertain significance Bloom syndrome 2024-07-19 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1118 of the BLM protein (p.Phe1118Leu). This variant is not present in population databases (gnomAD no frequency). 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: 524769). 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 RCV002325191 SCV002607157 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-06 criteria provided, single submitter clinical testing The c.3354C>A (p.F1118L) alteration is located in exon 17 (coding exon 16) of the BLM gene. This alteration results from a C to A substitution at nucleotide position 3354, causing the phenylalanine (F) at amino acid position 1118 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV005000394 SCV005624268 uncertain significance not provided 2024-01-25 criteria provided, single submitter clinical testing The BLM c.3354C>A (p.Phe1118Leu) variant has not been reported in individuals with BLM-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000628630 SCV002090552 uncertain significance Bloom syndrome 2019-02-04 no assertion criteria provided clinical testing

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