ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1436T>G (p.Phe479Cys)

gnomAD frequency: 0.00001  dbSNP: rs1418071613
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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 RCV000542996 SCV000623238 uncertain significance Bloom syndrome 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 479 of the BLM protein (p.Phe479Cys). This variant is present in population databases (no rsID available, 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: 454077). 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. 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.
Baylor Genetics RCV000542996 SCV002030128 uncertain significance Bloom syndrome 2021-07-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002395270 SCV002696243 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-05 criteria provided, single submitter clinical testing The p.F479C variant (also known as c.1436T>G), located in coding exon 6 of the BLM gene, results from a T to G substitution at nucleotide position 1436. The phenylalanine at codon 479 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly 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.
Natera, Inc. RCV000542996 SCV001460782 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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