Total submissions: 14
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genome- |
RCV002290035 | SCV002583065 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV001021045 | SCV002582404 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000786840 | SCV002498240 | pathogenic | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000786840 | SCV001805078 | pathogenic | not provided | 2019-10-17 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in an in-frame deletion of a critical region: disrupts the transactivation domain, nuclear export signals, SH3 domain, and DNA binding domain (Zhang 2001, Bode 2004, Pessoa 2014); Published functional studies demonstrate a damaging effect: aberrant splicing (Smardova 2016); Not observed in large population cohorts (Lek 2016); Identified in patients with personal or family history consistent with pathogenic variants in this gene referred for genetic testing at GeneDx; A different variant affecting the same splice site (c.375G>A) has been reported as pathogenic at GeneDx in association with Li-Fraumeni syndrome and shown to result in a similar splicing impact (Varley 2001, Bougeard 2008, Hettmer 2014, Wasserman 2015); This variant is associated with the following publications: (PMID: 26718964, 28807936) |
| Ambry Genetics | RCV001021045 | SCV001182608 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2025-03-20 | criteria provided, single submitter | clinical testing | The c.375+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 3 of the TP53 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however direct evidence is insufficient at this time (Ambry internal data). This variant has been reported in a pediatric patient meeting Chompret criteria with a personal history of rhabdomyosarcoma and family history of breast cancer; the variant was also identified in the patient's mother and sibling (Donato UM et al. Cureus, 2022 Jul;14:e27009). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. As such, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV000804919 | SCV000944857 | pathogenic | Li-Fraumeni syndrome | 2025-01-07 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 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 clinical features of Li-Fraumeni syndrome (PMID: 7887414, 17224268; internal data). ClinVar contains an entry for this variant (Variation ID: 635393). 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. |
| Dr. |
RCV005901928 | SCV006902804 | not provided | Adrenocortical carcinoma, hereditary | no classification provided | in vitro | ||
| Dr. |
RCV005901929 | SCV006902803 | not provided | Gastric cancer | no classification provided | in vitro | ||
| Dr. |
RCV005901930 | SCV006902802 | not provided | Ovarian serous cystadenocarcinoma | no classification provided | in vitro | ||
| Dr. |
RCV005901930 | SCV006902801 | not provided | Ovarian serous cystadenocarcinoma | no classification provided | in vitro | ||
| Dr. |
RCV005901930 | SCV006902800 | not provided | Ovarian serous cystadenocarcinoma | no classification provided | in vitro | ||
| Dr. |
RCV005901927 | SCV006902799 | not provided | Squamous cell carcinoma of the head and neck | no classification provided | in vitro | ||
| Dr. |
RCV005901926 | SCV006902798 | not provided | Familial cancer of breast | no classification provided | in vitro | ||
| Mut |
RCV000786840 | SCV000925736 | not provided | not provided | no classification provided | in vitro |