ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4319A>G (p.Glu1440Gly) (rs786202288)

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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 RCV000165024 SCV000215721 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000237052 SCV000293962 uncertain significance not provided 2016-02-12 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4319A>G at the cDNA level, p.Glu1440Gly (E1440G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAG>GGG). Using alternate nomenclature, this variant would be defined as BRCA1 4438A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu1440Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1440Gly occurs at a position that is not conserved and is located in a region known to interact with multiple proteins (Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Glu1440Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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