ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3893C>T (p.Ser1298Leu) (rs80357440)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235595 SCV000293247 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3893C>T at the cDNA level, p.Ser1298Leu (S1298L) at the protein level, and results in the change of a Serine to a Leucine (TCA>TTA). Using alternate nomenclature, this variant would be defined as BRCA1 4012C>T. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRCA1 Ser1298Leu 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 Serine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Ser1298Leu occurs at a position that is conserved across species and is located in the DNA Binding Domain and a region known to interact with multiple other proteins (Narod 2004, 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 Ser1298Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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