ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5098A>G (p.Thr1700Ala) (rs397509227)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519293 SCV000617448 likely pathogenic not provided 2018-07-25 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5098A>G at the cDNA level, p.Thr1700Ala (T1700A) at the protein level, and results in the change of a Threonine to an Alanine (ACA>GCA). Using alternate nomenclature, this variant has been previously published as BRCA1 5217A>G. Functional studies have found this variant to cause decreased phosphopeptide binding, binding specificity, and transactivation (Carvalho 2007, Lee 2010, Coquelle 2011). Of note, Coquelle et al. (2011) found BRCA1 T1700A to impact binding to the BACH1 phosphopeptide, a known binding partner of BRCA1. BRCA1 Thr1700Ala was not observed in large population cohorts (Lek 2016). This variant is located in the BRCT1 domain and a region known to interact with multiple other proteins (Paul 2014, UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, we consider BRCA1 Thr1700Ala to be a likely pathogenic variant.

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