ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3991A>G (p.Arg1331Gly) (rs150631940)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000536540 SCV000898549 uncertain significance Bloom syndrome 2017-12-18 criteria provided, single submitter clinical testing BLM NM_000057.3 exon 21 p.Arg1331Gly (c.3991A>G):This variant has not been reported in the literature but is present in 5/24038 African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs150631940). This variant is present in ClinVar (Variation ID:127507). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Functional studies suggest that this variant may not impact the protein (Mirzaei 2012 PMID:231296269). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV000115315 SCV000149224 uncertain significance not provided 2014-02-28 criteria provided, single submitter clinical testing Single pathogenic variants in BLM have only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted BLM c.3991A>G at the cDNA level, p.Arg1331Gly (R1331G) at the protein level, and results in the change of an Arginine to a Glycine (AGA>GGA). A functional study found that yeast cells expressing this variant have similar sensitivity to a DNA-damaging agent as compared to wild type (Mirzaei 2012). BLM Arg1331Gly was not observed at a significant allele frequency in 1000 Genomes or the NHLBI Exome Sequencing Project. Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution and is likely to affect protein integrity. BLM Arg1331Gly occurs at a position that is moderately conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BLM Arg1331Gly is pathogenic or benign. We consider it to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants the BLM gene in general, remain unclear.
Invitae RCV000536540 SCV000623326 uncertain significance Bloom syndrome 2018-03-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 1331 of the BLM protein (p.Arg1331Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs150631940, ExAC 0.04%). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 127507). Experimental studies have shown that this missense change does not affect protein function using a yeast model (PMID: 23129629). 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.
Mendelics RCV000536540 SCV000838988 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.