ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3170G>A (p.Ser1057Asn) (rs587776487)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485904 SCV000570103 uncertain significance not provided 2017-04-24 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3170G>A at the cDNA level, p.Ser1057Asn (S1057N) at the protein level, and results in the change of a Serine to an Asparagine (AGT>AAT). Using alternate nomenclature, this variant would be defined as BRCA1 3289G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Ser1057Asn was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Serine and Asparagine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Ser1057Asn occurs at a position that is not conserved and is located in the DNA Binding domain as well as a region of interaction with RAD51 (Narod 2004, Chen 1998). 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 Ser1057Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000563435 SCV000665905 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000563435 SCV000688424 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000704884 SCV000833856 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-11 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 1057 of the BRCA1 protein (p.Ser1057Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs587776487, ExAC 0.001%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 156191). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Sharing Clinical Reports Project (SCRP) RCV000144208 SCV000189281 uncertain significance Breast-ovarian cancer, familial 1 2008-02-14 no assertion criteria provided clinical testing

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