ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3341_3343AAG[1] (p.Glu1115del) (rs80358336)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129777 SCV000184586 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000513128 SCV000210039 uncertain significance not provided 2017-11-29 criteria provided, single submitter clinical testing This in-frame deletion of three nucleotides in BRCA1 is denoted c.3344_3346delAAG at the cDNA level and p.Glu1115del (E1115del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GAAG[delAAG]TAGT. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion of a single Glutamic Acid amino acid is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BRCA1 Glu1115del to be a variant of uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513128 SCV000608816 uncertain significance not provided 2017-02-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000513128 SCV000699022 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The c.3344_3346delAAG (p.Glu1115del) in BRCA1 gene leads to an in-frame deletion of Glu amino acid from a non-repeat region that is located outside of any known functional domain. The variant is present in the control population dataset of ExAC at frequency of 2.477e-05 (3/121130 chrs tested). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, however UMD cites co-occurrence of the variant with a BRCA2 pathogenic mutation (c.5909C>A, p.Ser1970X). In addition, multiple reputable databases/clinical laboratories have classified the variant as VUS. Taking together, the variant was classified as VUS.
Invitae RCV000793753 SCV000933122 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-29 criteria provided, single submitter clinical testing This variant, c.3344_3346delAAG, results in the deletion of 1 amino acid of the BRCA1 protein (p.Glu1115del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs80358336, ExAC 0.004%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 54852). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112075 SCV000144731 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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