ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.577T>C (p.Phe193Leu)

gnomAD frequency: 0.00001  dbSNP: rs779348937
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701183 SCV000829969 uncertain significance Bloom syndrome 2022-10-04 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 193 of the BLM protein (p.Phe193Leu). This variant is present in population databases (rs779348937, gnomAD 0.01%). 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: 578232). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001024525 SCV001186555 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-05 criteria provided, single submitter clinical testing The p.F193L variant (also known as c.577T>C), located in coding exon 2 of the BLM gene, results from a T to C substitution at nucleotide position 577. The phenylalanine at codon 193 is replaced by leucine, an amino acid with highly similar 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000701183 SCV004171453 uncertain significance Bloom syndrome 2023-09-22 criteria provided, single submitter clinical testing The BLM c.577T>C (p.Phe193Leu) missense change has a maximum subpopulation frequency of 0.01% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. ?In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.?
Natera, Inc. RCV000701183 SCV001456644 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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