ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1387G>A (p.Val463Ile)

gnomAD frequency: 0.00003  dbSNP: rs1028963834
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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 RCV000814390 SCV000954799 uncertain significance Bloom syndrome 2022-08-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 463 of the BLM protein (p.Val463Ile). 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: 657721). 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 isoleucine 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 RCV001011214 SCV001171511 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-27 criteria provided, single submitter clinical testing The p.V463I variant (also known as c.1387G>A), located in coding exon 6 of the BLM gene, results from a G to A substitution at nucleotide position 1387. The valine at codon 463 is replaced by isoleucine, an amino acid with highly similar 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. RCV000814390 SCV002090032 uncertain significance Bloom syndrome 2021-01-14 no assertion criteria provided clinical testing

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