ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2299A>G (p.Ser767Gly) (rs80357194)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047788 SCV000075801 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 767 of the BRCA1 protein (p.Ser767Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 37461). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Ambry Genetics RCV000130067 SCV000184894 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000485116 SCV000565778 uncertain significance not provided 2015-03-20 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2299A>G at the cDNA level, p.Ser767Gly (S767G) at the protein level, and results in the change of a Serine to a Glycine (AGC>GGC). Using alternate nomenclature, this variant has been previously published as BRCA1 2418A>G. This variant was observed once in a series of breast cancers and was predicted unlikely to interfere with protein function based on a protein alignment algorithm (Borg 2010). BRCA1 Ser767Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Ser767Gly occurs at a position that is not conserved across species and is located in the DNA binding domain (Narod 2004). 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 Ser767Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000130067 SCV000909348 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031042 SCV000053636 uncertain significance Breast-ovarian cancer, familial 1 2008-03-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031042 SCV000144371 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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