Submissions for variant NM_007294.4(BRCA1):c.1021G>A (p.Asp341Asn)

dbSNP: rs756987689

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000461312	SCV000549409	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 341 of the BRCA1 protein (p.Asp341Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 18273839). ClinVar contains an entry for this variant (Variation ID: 409364). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758783	SCV000887618	uncertain significance	not provided	2022-10-04	criteria provided, single submitter	clinical testing	It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in families with breast or ovarian cancer (PMID: 18273839 (2008)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health	RCV000775726	SCV000910149	uncertain significance	Hereditary cancer-predisposing syndrome	2019-06-22	criteria provided, single submitter	clinical testing
Mendelics	RCV000989905	SCV001140613	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000775726	SCV001178053	uncertain significance	Hereditary cancer-predisposing syndrome	2018-07-22	criteria provided, single submitter	clinical testing	The p.D341N variant (also known as c.1021G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1021. The aspartic acid at codon 341 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been detected in a cohort of French breast and/or ovarian cancer families (Anczuków O et al. Genes Chromosomes Cancer, 2008 May;47:418-26). 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	RCV000758783	SCV002575799	uncertain significance	not provided	2022-03-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1140G>A; This variant is associated with the following publications: (PMID: 10426999, 20215511, 15343273, 9926942, 9582019, 11521194)
University of Washington Department of Laboratory Medicine, University of Washington	RCV000775726	SCV003846225	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).