ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4654T>C (p.Tyr1552His) (rs1265352633)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504104 SCV000591531 uncertain significance not specified 2014-10-27 criteria provided, single submitter clinical testing
Invitae RCV000532651 SCV000635985 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 1552 of the BRCA1 protein (p.Tyr1552His). The tyrosine residue is weakly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer and cutaneous malignant melanoma (PMID: 22713736, 29036293). This variant is also known as 4773T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 433716). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The histidine 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. 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 RCV000758836 SCV000887705 uncertain significance not provided 2018-11-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765359 SCV000896624 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000776618 SCV000912236 likely benign Hereditary cancer-predisposing syndrome 2017-10-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000776618 SCV001184632 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-08 criteria provided, single submitter clinical testing Insufficient evidence
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735520 SCV000863658 likely benign Breast and/or ovarian cancer 2013-10-03 no assertion criteria provided clinical testing

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