ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2611_2612delinsGT (p.Pro871Val) (rs1064793056)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480523 SCV000564729 uncertain significance not specified 2014-10-24 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2611_2612delCCinsGT at the cDNA level, p.Pro871Val (P871V) at the protein level. The normal sequence, with the bases that are deleted and inserted in brackets, is TGCT[delCCinsGT]GTTT. This in frame deletion and insertion occurs on the same allele (in cis) and results in the missense change of a Proline to a Valine (CCG>GTG). This variant has not, to our knowledge, been published in the literature as either a mutation or benign polymorhism. BRCA1 Pro871Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Proline and Valine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Pro871Val occurs at a position that is highly variable across species and is located in the DNA-binding domain (Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, we consider BRCA1 Pro871Val to be a variant of uncertain significance.
Invitae RCV000821444 SCV000962200 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline with valine at codon 871 of the BRCA1 protein (p.Pro871Val). The proline residue is weakly conserved and there is a small physicochemical difference between proline and valine. 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: 418068). 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.
Ambry Genetics RCV001016099 SCV001177014 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-01 criteria provided, single submitter clinical testing In silico models in agreement (benign);Insufficient evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes)

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