ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2069C>T (p.Pro690Leu) (rs761589072)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000535832 SCV000793320 uncertain significance Bloom syndrome 2017-08-10 criteria provided, single submitter clinical testing
Invitae RCV000535832 SCV000623257 uncertain significance Bloom syndrome 2017-07-17 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 690 of the BLM protein (p.Pro690Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs761589072, ExAC 0.01%). This variant has been reported as heterozygous in an individual affected with bloom syndrome. However the second allele is not mentioned in the report (PMID: 17407155). Experimental studies have shown that this missense change disrupts BLM protein function and an inefficient DNA repair process in yeast and patient's fibroblasts (PMID: 23129629, 2678854). 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.

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