ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4130T>C (p.Ile1377Thr)

gnomAD frequency: 0.00001  dbSNP: rs1555425416
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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 RCV000531472 SCV000623334 uncertain significance Bloom syndrome 2024-09-03 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1377 of the BLM protein (p.Ile1377Thr). 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: 454150). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine 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 RCV001021923 SCV001183600 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-24 criteria provided, single submitter clinical testing The p.I1377T variant (also known as c.4130T>C), located in coding exon 21 of the BLM gene, results from a T to C substitution at nucleotide position 4130. The isoleucine at codon 1377 is replaced by threonine, an amino acid with 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. RCV000531472 SCV002090662 uncertain significance Bloom syndrome 2020-07-15 no assertion criteria provided clinical testing

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