ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4059T>A (p.Ser1353Arg)

gnomAD frequency: 0.00001  dbSNP: rs1060500646
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472912 SCV000543372 uncertain significance Bloom syndrome 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1353 of the BLM protein (p.Ser1353Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 405309). 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 with a negative 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 RCV001021769 SCV001183426 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-30 criteria provided, single submitter clinical testing The p.S1353R variant (also known as c.4059T>A), located in coding exon 20 of the BLM gene, results from a T to A substitution at nucleotide position 4059. The serine at codon 1353 is replaced by arginine, an amino acid with 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.
Sema4, Sema4 RCV001021769 SCV002533007 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-06 criteria provided, single submitter curation
Natera, Inc. RCV000472912 SCV001461026 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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