ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3040A>T (p.Met1014Leu) (rs80356933)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482931 SCV000571631 uncertain significance not provided 2016-09-08 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3040A>T at the cDNA level, p.Met1014Leu (M1014L) at the protein level, and results in the change of a Methionine to a Leucine (ATG>TTG). Using alternate nomenclature, this variant would be defined as BRCA1 3159A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Met1014Leu 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 Methionine and Leucine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Met1014Leu occurs at a position that is not conserved and is located in the RAD51 binding domain (Chen 1998). 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 Met1014Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000564207 SCV000665899 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000111988 SCV000144618 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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