Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165729 | SCV000216470 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-08-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000474546 | SCV000549402 | uncertain significance | Hereditary breast and ovarian cancer syndrome | 2018-11-11 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 17 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs375639469, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 91639). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. |
Integrated Genetics/Laboratory Corporation of America | RCV000588488 | SCV000699214 | uncertain significance | not provided | 2017-01-03 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.5153-3T>C variant involves the alteration of a non-conserved intronic nucleotide, which 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/119938, which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, although multiple clinical diagnostic laboratories classify the variant as "uncertain significance." Therefore, until additional information becomes available (ie, clinical and/or functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)." |
Gene |
RCV000616210 | SCV000730671 | likely benign | not specified | 2017-07-28 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Color | RCV000165729 | SCV000912006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-30 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000077156 | SCV000108953 | uncertain significance | Breast-ovarian cancer, familial 1 | 2009-10-13 | no assertion criteria provided | clinical testing |