ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1573G>A (p.Val525Ile) (rs80357273)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047530 SCV000075543 likely benign Hereditary breast and ovarian cancer syndrome 2020-09-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000214482 SCV000273956 likely benign Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000417626 SCV000512287 likely benign not specified 2018-03-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Health, Inc RCV000214482 SCV000903404 likely benign Hereditary cancer-predisposing syndrome 2016-01-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000417626 SCV000916761 uncertain significance not specified 2018-06-18 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1573G>A (p.Val525Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 276034 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1573G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer and pancreatic cancer. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments, including VUS (1x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as VUS.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985370 SCV001133490 uncertain significance not provided 2019-07-25 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077491 SCV000109289 likely benign Breast-ovarian cancer, familial 1 2009-06-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077491 SCV000144135 uncertain significance Breast-ovarian cancer, familial 1 2006-07-19 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000985370 SCV000591343 likely benign not provided no assertion criteria provided clinical testing The BRCA1 p.Val525Ile variant was identified by Solano (2012) in an individual referred for testing due to early onset of breast or ovarian cancer or a family history of breast or ovarian cancer. The variant was also identified in dbSNP (ID: rs80357273) the BIC database (1X with unknown clinical importance), and UMD (1X as an unclassified variant). The variant was classified as likely benign by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The p.Val525 residue is not conserved in mammals and the variant amino acid isoleucine (Ile) is present in chicken, increasing the likelihood that this variant does not have clinical significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.

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