ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3014T>C (p.Ile1005Thr)

gnomAD frequency: 0.00001  dbSNP: rs772671554
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneKor MSA RCV000708667 SCV000821902 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000810866 SCV000951103 uncertain significance Bloom syndrome 2024-01-18 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 1005 of the BLM protein (p.Ile1005Thr). This variant is present in population databases (rs772671554, gnomAD 0.002%). 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: 584503). 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 expected to disrupt BLM protein function with a positive predictive value of 80%. 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 RCV000708667 SCV001179244 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-31 criteria provided, single submitter clinical testing The p.I1005T variant (also known as c.3014T>C), located in coding exon 14 of the BLM gene, results from a T to C substitution at nucleotide position 3014. The isoleucine at codon 1005 is replaced by threonine, an amino acid with similar properties. This alteration has been identified in a cohort of 130 Romanian breast cancer patients (Goidescu IG et al. Clujul Med, 2018 Apr;91:157-165). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000810866 SCV002090503 uncertain significance Bloom syndrome 2020-02-17 no assertion criteria provided clinical testing

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