Submissions for variant NM_007294.4(BRCA1):c.1713A>G (p.Ile571Met)

gnomAD frequency: 0.00001  dbSNP: rs552505690

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165574	SCV000216308	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-27	criteria provided, single submitter	clinical testing	The p.I571M variant (also known as c.1713A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1713. The isoleucine at codon 571 is replaced by methionine, an amino acid with highly similar properties. 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.
Invitae	RCV000458990	SCV000549367	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-10-31	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 571 of the BRCA1 protein (p.Ile571Met). This variant is present in population databases (rs552505690, gnomAD 0.007%). 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: 186051). 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.
Counsyl	RCV000662805	SCV000785638	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2017-10-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165574	SCV000903892	likely benign	Hereditary cancer-predisposing syndrome	2016-05-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985373	SCV001133495	uncertain significance	not provided	2021-04-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000985373	SCV003845498	uncertain significance	not provided	2023-03-22	criteria provided, single submitter	clinical testing	Observed in individuals undergoing multi-gene panel testing based on personal and family history of cancer (Li et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 1832A>G; This variant is associated with the following publications: (PMID: 31911673, 32377563, 29884841, 30630528, 31853058, 15343273, 10792030, 10426999)
University of Washington Department of Laboratory Medicine, University of Washington	RCV000165574	SCV003851089	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).