ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1315A>G (p.Met439Val) (rs201231857)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115281 SCV000149190 uncertain significance not provided 2014-03-04 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.1315A>G at the cDNA level, p.Met439Val (M439V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Met439Val was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Methionine and Valine share similar properties, this is considered a conservative amino acid substitution and is unlikely to affect protein integrity. BLM Met439Val occurs at a position that is highly variable across species and is located in the region necessary for interaction with Scaffolding Protein Involved in DNA Repair- SPIDR- (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on the currently available information, we consider BLM Met439Val 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 RCV000234473 SCV000283112 benign Bloom syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000574443 SCV000672900 likely benign Hereditary cancer-predisposing syndrome 2018-10-30 criteria provided, single submitter clinical testing Other strong data supporting benign classification;In silico models in agreement (benign)
GeneKor MSA RCV000574443 SCV000821793 likely benign Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000234473 SCV000838958 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000234473 SCV001275084 uncertain significance Bloom syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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