ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3842A>C (p.Gln1281Pro) (rs80357483)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000112198 SCV000488929 uncertain significance Breast-ovarian cancer, familial 1 2016-07-21 criteria provided, single submitter clinical testing
GeneDx RCV000484233 SCV000565975 uncertain significance not provided 2015-09-17 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3842A>C at the cDNA level, p.Gln1281Pro (Q1281P) at the protein level, and results in the change of a Glutamine to a Proline (CAG>CCG). Using alternate nomenclature, this variant has been previously published as BRCA1 3961A>C. This variant has been reported in at least one individual undergoing BRCA1/2 analysis at a commercial laboratory and was predicted to abolish the kinase binding motif resulting in the loss of the phosphorylation site at Ser1280 (Judkins 2005, Tram 2013). BRCA1 Gln1281Pro was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glutamine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Gln1281Pro occurs at a position that is not conserved and is located in the SCD 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 information, it is unclear whether BRCA1 Gln1281Pro is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000775153 SCV000909290 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112198 SCV000144895 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing

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