ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2263G>A (p.Glu755Lys) (rs41286296)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216413 SCV000273530 uncertain significance Hereditary cancer-predisposing syndrome 2015-08-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000483305 SCV000564724 uncertain significance not provided 2017-04-14 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2263G>A at the cDNA level, p.Glu755Lys (E755K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). Using alternate nomenclature, this variant would be defined as BRCA1 2382G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu755Lys was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu755Lys occurs at a position that is not conserved and is located within the DNA-binding domain as well as a region that binds STAT1 (Ouchi 2000, Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA1 Glu755Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.

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