ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2527A>G (p.Thr843Ala) (rs80357435)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480963 SCV000572907 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2527A>G at the cDNA level, p.Thr843Ala (T843A) at the protein level, and results in the change of a Threonine to an Alanine (ACA>GCA). Using alternate nomenclature, this variant would be defined as BRCA1 2646A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Thr843Ala 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 Threonine and Alanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Thr843Ala occurs at a position that is not conserved and is located in the DNA binding domain that interacts with RAD51 (Chen 1998, Narod 2004). 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 Thr843Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111884 SCV000144468 uncertain significance Breast-ovarian cancer, familial 1 1997-11-14 no assertion criteria provided clinical testing

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