ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3224G>A (p.Arg1075Lys)

dbSNP: rs749559270
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000803505 SCV000943383 uncertain significance Bloom syndrome 2020-01-11 criteria provided, single submitter clinical testing 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. 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 lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BLM-related disease. This variant is present in population databases (rs749559270, ExAC 0.002%). This sequence change replaces arginine with lysine at codon 1075 of the BLM protein (p.Arg1075Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine.
Ambry Genetics RCV001019310 SCV001180649 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-16 criteria provided, single submitter clinical testing The p.R1075K variant (also known as c.3224G>A), located in coding exon 16 of the BLM gene, results from a G to A substitution at nucleotide position 3224. The arginine at codon 1075 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is well 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.

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