ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2882A>G (p.Asn961Ser) (rs879254130)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235761 SCV000293594 uncertain significance not provided 2018-03-05 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2882A>G at the cDNA level, p.Asn961Ser (N961S) at the protein level, and results in the change of an Asparagine to a Serine (AAC>AGC). Using alternate nomenclature, this variant would be defined as BRCA1 3001A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Asn961Ser was not observed in large population cohorts (Lek 2016). This variant is located in the RAD51 and DNA binding domain (Chen 1998, Narod 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Asn961Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000575733 SCV000668449 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000701306 SCV000830100 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 961 of the BRCA1 protein (p.Asn961Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 246160). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000575733 SCV000905075 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-30 criteria provided, single submitter clinical testing

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