ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3587C>T (p.Thr1196Ile) (rs80356944)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048242 SCV000076255 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-22 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1196 of the BRCA1 protein (p.Thr1196Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with breast and/or ovarian cancer (PMID: 29297111, 27211102, 24372583). ClinVar contains an entry for this variant (Variation ID: 54926). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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 RCV000112127 SCV000296448 uncertain significance Breast-ovarian cancer, familial 1 2016-03-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509865 SCV000607830 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-16 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
Counsyl RCV000112127 SCV000785250 uncertain significance Breast-ovarian cancer, familial 1 2017-06-13 criteria provided, single submitter clinical testing
Color RCV000509865 SCV000909298 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779887 SCV000916774 uncertain significance not specified 2018-06-28 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3587C>T (p.Thr1196Ile) 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 4.1e-06 in 245648 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.3587C>T, has been reported in the literature in an individual affected with Hereditary Breast and Ovarian Cancer (Riahi_2015, Riahi_2016). These report(s) 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 ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001092620 SCV001249203 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000112127 SCV001284949 uncertain significance Breast-ovarian cancer, familial 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112127 SCV000144799 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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