ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4240T>C (p.Tyr1414His)

gnomAD frequency: 0.00003  dbSNP: rs753800694
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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 RCV000532261 SCV000623337 uncertain significance Bloom syndrome 2025-02-02 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1414 of the BLM protein (p.Tyr1414His). This variant is present in population databases (rs753800694, 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: 454153). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV000571399 SCV000672902 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-20 criteria provided, single submitter clinical testing The p.Y1414H variant (also known as c.4240T>C), located in coding exon 21 of the BLM gene, results from a T to C substitution at nucleotide position 4240. The tyrosine at codon 1414 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV005000111 SCV005624284 uncertain significance not provided 2024-10-02 criteria provided, single submitter clinical testing The BLM c.4240T>C (p.Tyr1414His) variant has been reported in the published literature in an individual with prostate cancer (PMID: 29659569 (2018)). The frequency of this variant in the general population, 0.000016 (4/251452 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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 benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000532261 SCV001461033 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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