Submissions for variant NM_007294.4(BRCA1):c.3080G>C (p.Ser1027Thr)

dbSNP: rs80357386

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001328037	SCV000698993	uncertain significance	not specified	2021-03-14	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.3080G>C (p.Ser1027Thr) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251110 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3080G>C in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587381	SCV000887658	uncertain significance	not provided	2018-04-05	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764121	SCV000895094	uncertain significance	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001018505	SCV001179752	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-18	criteria provided, single submitter	clinical testing	The c.3080G>C (p.S1027T) alteration is located in exon 10 (coding exon 9) of the BRCA1 gene. This alteration results from a G to C substitution at nucleotide position 3080, causing the serine (S) at amino acid position 1027 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001053353	SCV001217611	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-09-08	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1027 of the BRCA1 protein (p.Ser1027Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 496362). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. 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 Diagnostics, LLC DBA Color Health	RCV001018505	SCV001351501	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-15	criteria provided, single submitter	clinical testing	This missense variant replaces serine with threonine at codon 1027 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
University of Washington Department of Laboratory Medicine, University of Washington	RCV001018505	SCV003849139	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health	RCV004002446	SCV004815607	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2023-06-26	criteria provided, single submitter	clinical testing	This missense variant replaces serine with threonine at codon 1027 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Breakthrough Genomics, Breakthrough Genomics	RCV000587381	SCV005192893	uncertain significance	not provided		criteria provided, single submitter	not provided