Submissions for variant NM_007294.4(BRCA1):c.3601G>A (p.Gly1201Ser)

gnomAD frequency: 0.00001  dbSNP: rs55725337

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000048248	SCV000076261	likely benign	Hereditary breast ovarian cancer syndrome	2023-12-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000166259	SCV000217039	likely benign	Hereditary cancer-predisposing syndrome	2018-12-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000166259	SCV000912036	likely benign	Hereditary cancer-predisposing syndrome	2018-03-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780976	SCV000918694	likely benign	not specified	2023-06-01	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.3601G>A (p.Gly1201Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250998 control chromosomes. c.3601G>A has been reported in the literature in at least two individuals affected with cancer without strong evidence for causality (e.g., Salazar_2006, Matta_2022). Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.4251_4252delGT, p.Leu1418ArgfsX9; BRCA1 c.4998C>A , p.Tyr1666X; BRCA2 c.1138_1138delA, p.Ser380Valfs), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function (Bouwman_2020). These results showed no damaging effect of this variant on ability to complement BRCA1-deficient mouse embryonic stem cells in homologous recombination DNA repair (HRR) using cisplatin and olaparib sensitivity assays and a direct GFP HRR assay. The following publications have been ascertained in the context of this evaluation (PMID: 15385441, 15876480, 23704879, 25348012, 34749799, 32546644, 33087888, 36329109). Seven ClinVar submitters have submitted clinical-significance assessments for this variant to ClinVar after 2014. Six submitters classified the variant as likely benign and one classified it as benign. Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001283901	SCV001469387	likely benign	not provided	2020-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001283901	SCV001823529	likely benign	not provided	2020-08-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 15876480, 33087888, 31131967)
Genetics Program, Instituto Nacional de Cancer	RCV000048248	SCV002515201	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Mendelics	RCV000780976	SCV002516958	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112131	SCV000144804	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1999-04-05	no assertion criteria provided	clinical testing