Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Myriad Genetics, |
RCV002289678 | SCV004930469 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-14 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Baylor Genetics | RCV003476180 | SCV004204286 | likely pathogenic | Adrenocortical carcinoma, hereditary | 2021-11-26 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV002289678 | SCV002583039 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000492159 | SCV002582378 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000786834 | SCV002005066 | pathogenic | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29470806, 30720243, 30212483, 27619989, 37377903, 26911350, 32817165, 35014770) |
| Labcorp Genetics |
RCV001210960 | SCV001382477 | pathogenic | Li-Fraumeni syndrome | 2024-12-04 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 of the TP53 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Li-Fraumeni syndrome, breast cancer, and acute lymphoblastic leukemia (PMID: 23484829, 23894400, 26911350, 27619989, 30212483). ClinVar contains an entry for this variant (Variation ID: 428908). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ce |
RCV000786834 | SCV001247048 | pathogenic | not provided | 2018-11-01 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000763418 | SCV000894155 | pathogenic | Adrenocortical carcinoma, hereditary; Familial cancer of breast; Glioma susceptibility 1; Bone osteosarcoma; Li-Fraumeni syndrome 1; Nasopharyngeal carcinoma; Carcinoma of pancreas; Choroid plexus papilloma; Carcinoma of colon; Basal cell carcinoma, susceptibility to, 7; Hepatocellular carcinoma | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000492159 | SCV000581171 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-10-25 | criteria provided, single submitter | clinical testing | The c.559+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 4 of the TP53 gene. This alteration has been reported in a woman diagnosed at age 46 with breast cancer and synchronous pleomorphic leiomyosarcoma (Mannan AU et al. J. Hum. Genet., 2016 Jun;61:515-22). It was also identified in an Indian breast/ovarian cancer cohort (Singh J et al. Breast Cancer Res. Treat. 2018 Jul;170(1):189-196) and in a woman with two breast cancers before age 30 (Wang PY et al. N Engl J Med, 2013 Mar;368:1027-32). In addition, this variant has been reported as a germline alteration and as a somatic alteration in various tumors by the IARC TP53 database (Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum Mutat. 2007 Jun;28(6):622-9). This variant has been detected in at least one individual at an allele fraction that is suggestive of clonal hematopoiesis, a predictor of TP53 pathogenicity (Ambry internal data; Fortuno C et al. Genet Med. 2022 03;24:673-680). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site; however, however direct evidence is insufficient at this time (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is interpreted as a disease-causing mutation. |
| Mut |
RCV000786834 | SCV000925728 | not provided | not provided | no assertion provided | in vitro |