ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3841C>G (p.Gln1281Glu)

dbSNP: rs80356866
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482543 SCV000570105 uncertain significance not provided 2018-03-16 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3841C>G at the cDNA level, p.Gln1281Glu (Q1281E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAG>GAG). Using alternate nomenclature, this variant would be defined as BRCA1 3960C>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1281Glu was not observed in large population cohorts (Lek 2016). This variant is located in SCD domain and in the binding domain of ATM, CHK2 and CDK2 (Narod 2004, Clark 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Gln1281Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV002367638 SCV002624659 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-30 criteria provided, single submitter clinical testing The p.Q1281E variant (also known as c.3841C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3841. The glutamine at codon 1281 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002367638 SCV003851324 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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