ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3358G>A (p.Val1120Ile) (rs748894760)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163154 SCV000213671 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000200265 SCV000254972 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1120 of the BRCA1 protein (p.Val1120Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 184039). 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 isoleucine 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.
GeneDx RCV000235337 SCV000293908 uncertain significance not provided 2018-04-17 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3358G>A at the cDNA level, p.Val1120Ile (V1120I) at the protein level, and results in the change of a Valine to an Isoleucine (GTT>ATT). Using alternate nomenclature, this variant would be defined as BRCA1 3477G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Val1120Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Val1120Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000410885 SCV000488703 uncertain significance Breast-ovarian cancer, familial 1 2016-10-18 criteria provided, single submitter clinical testing
Color RCV000163154 SCV000688431 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing

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