ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.32T>G (p.Val11Gly) (rs80357017)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236530 SCV000293217 uncertain significance not provided 2016-09-27 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.32T>G at the cDNA level, p.Val11Gly (V11G) at the protein level, and results in the change of a Valine to a Glycine (GTA>GGA). Using alternate nomenclature, this variant would be defined as BRCA1 151T>G. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRCA1 Val11Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Glycine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Val11Gly occurs at a position that is conserved through mammals and is located in the RING domain and the regions of interaction with BRD7 and BARD1 (Narod 2004, Borg 2010, Harte 2010, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Val11Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000509835 SCV000608110 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-12 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000792051 SCV000931323 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-05 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 11 of the BRCA1 protein (p.Val11Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. 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: 245973). 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 disruptive, 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.
Brotman Baty Institute,University of Washington RCV001072350 SCV001237715 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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