ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3355A>T (p.Thr1119Ser) (rs80356949)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048162 SCV000076175 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-02-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1119 of the BRCA1 protein (p.Thr1119Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs80356949, ExAC 0.001%). This variant has been observed in individuals in the Breast Cancer Information Core database (PMID: 10923033). However, in one of those individuals a pathogenic allele was also identified in BRCA2, which suggests that this c.3355A>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 54855). 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.
Ambry Genetics RCV000129260 SCV000184020 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-15 criteria provided, single submitter clinical testing The p.T1119S variant (also known as c.3355A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3355. The threonine at codon 1119 is replaced by serine, an amino acid with similar properties. This alteration has been detected in an individual with a personal and/or family history of breast and/or ovarian cancer (Judkins T et al. Cancer Res. 2005 Nov 1;65(21):10096-103). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000235634 SCV000292918 uncertain significance not provided 2020-08-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16267036, 31131967)
Color Health, Inc RCV000129260 SCV000906799 likely benign Hereditary cancer-predisposing syndrome 2016-09-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235634 SCV001133550 uncertain significance not provided 2018-12-21 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112078 SCV000144735 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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