Submissions for variant NM_007294.4(BRCA1):c.4405C>A (p.Pro1469Thr)

dbSNP: rs80356960

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000822315	SCV000963113	uncertain significance	Hereditary breast ovarian cancer syndrome	2018-10-16	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 1469 of the BRCA1 protein (p.Pro1469Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine.
Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research	RCV001090203	SCV001245501	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002259035	SCV002537748	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-05	criteria provided, single submitter	curation