ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3637G>A (p.Glu1213Lys)

gnomAD frequency: 0.00001  dbSNP: rs28385142
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569262 SCV000672956 likely benign Hereditary cancer-predisposing syndrome 2019-10-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga) RCV000727387 SCV000708117 uncertain significance not provided 2017-04-28 criteria provided, single submitter clinical testing
Invitae RCV001036176 SCV001199527 uncertain significance Bloom syndrome 2022-09-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1213 of the BLM protein (p.Glu1213Lys). This variant is present in population databases (rs28385142, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 133702). 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 not expected to disrupt BLM protein function. Experimental studies have shown that this missense change does not substantially affect BLM function (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.
Baylor Genetics RCV001036176 SCV001482839 uncertain significance Bloom syndrome 2020-02-23 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000727387 SCV004222486 uncertain significance not provided 2023-01-17 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.00011 (4/35436 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in unaffected individuals (PMID: 24728327 (2014)). A yeast based functional study has shown that this variant does not display sensitivity to a DNA damaging agent (PMID: 23129629 (2012)). However, additional studies are needed to determine the global effect of this variant on BLM protein function. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
ITMI RCV000120231 SCV000084378 not provided not specified 2013-09-19 no assertion provided reference population

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