Submissions for variant NM_007294.4(BRCA1):c.5258G>C (p.Arg1753Thr)

dbSNP: rs397509246

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759559	SCV000888945	pathogenic	not provided	2020-08-17	criteria provided, single submitter	clinical testing	A missense variant with dominant inheritance. Variant has been observed in multiple individuals with hereditary breast and ovarian cancer and one instance of male breast cancer (PMID 25066507, 19016756, internal patients), while not found in a large general population study (gnomAD dataset, and the data is high quality (0/277244 chr)). Located in a potentially critical domain of the protein. Damaging to protein function(s) relevant to disease mechanism (PMID: 30209399, 28781887, 23867111, 21447777, 20516115, 17308087). ClinVar contains an entry for this variant: 55488.
Color Diagnostics, LLC DBA Color Health	RCV000771309	SCV000903565	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-30	criteria provided, single submitter	clinical testing
Invitae	RCV001379222	SCV001576983	likely pathogenic	Hereditary breast ovarian cancer syndrome	2022-05-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1753 of the BRCA1 protein (p.Arg1753Thr). 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: 19016756, 25066507). ClinVar contains an entry for this variant (Variation ID: 55488). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 17308087, 20516115, 23867111, 30209399). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577271	SCV000679296	not provided	Familial cancer of breast		no assertion provided	literature only
Brotman Baty Institute, University of Washington	RCV001072582	SCV001237994	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001554320	SCV001775485	pathogenic	Breast carcinoma	2021-08-09	no assertion criteria provided	clinical testing