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

Minimum review status:		Collection method:
Minimum conflict level:
		ClinVar version:

Total submissions: 4

Download table as spreadsheet

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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.