ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2453G>A (p.Arg818His)

gnomAD frequency: 0.00001  dbSNP: rs780514723
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532627 SCV000623271 uncertain significance Bloom syndrome 2022-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 818 of the BLM protein (p.Arg818His). This variant is present in population databases (rs780514723, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. 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. 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 RCV001015590 SCV001176439 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-04 criteria provided, single submitter clinical testing The p.R818H variant (also known as c.2453G>A), located in coding exon 11 of the BLM gene, results from a G to A substitution at nucleotide position 2453. The arginine at codon 818 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000532627 SCV002088071 uncertain significance Bloom syndrome 2020-03-30 no assertion criteria provided clinical testing

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