ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4931A>G (p.Glu1644Gly) (rs80357016)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163234 SCV000213759 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
GeneDx RCV000235446 SCV000293971 uncertain significance not provided 2017-02-09 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4931A>G at the cDNA level, p.Glu1644Gly (E1644G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). Using alternate nomenclature, this variant would be defined as BRCA1 5050A>G. A transcriptional assay in yeast and mammalian cells found that this variant demonstrated transcription activation levels similar to wild type (Carvalho 2007). BRCA1 Glu1644Gly 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 Glu1644Gly occurs at a position that is not conserved and is located within the BRCT1 domain and a region known to interact with multiple other proteins (Paul 2014, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA1 Glu1644Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000163234 SCV000909004 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-06 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112422 SCV000145209 uncertain significance Breast-ovarian cancer, familial 1 2004-03-30 no assertion criteria provided clinical testing

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