Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000162396 | SCV000212719 | benign | Hereditary cancer-predisposing syndrome | 2014-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Labcorp Genetics |
RCV001085434 | SCV000253314 | likely benign | Li-Fraumeni syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000409816 | SCV000489223 | likely benign | Li-Fraumeni syndrome 1 | 2016-09-06 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000162396 | SCV000686759 | likely benign | Hereditary cancer-predisposing syndrome | 2015-04-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588456 | SCV000697445 | benign | not provided | 2017-07-21 | criteria provided, single submitter | clinical testing | Variant summary: The TP53 c.666G>T (p.Pro222Pro) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 12/277398 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000087 (11/126590). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), suggesting this is likely a benign polymorphism found primarily in population(s) of European (Non-Finnish) origin. Multiple publications have cited the variant as a somatic occurrence across varying cancers, however, germline analysis was not performed in these studies. A publication, Damineni_2014, does cite the variant, c.666G>C (p.Pro222Pro) as a germline occurrence in a BrC pt, however, limited information is provided (ie, no co-occurrence or cosegregation data and TP53 exons 5-9 were only assessed). In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign. Taken together, this variant is classified as benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588456 | SCV001134875 | benign | not provided | 2023-01-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000588456 | SCV001940211 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 29979965) |
CHEO Genetics Diagnostic Laboratory, |
RCV001798376 | SCV002042830 | likely benign | Breast and/or ovarian cancer | 2021-02-02 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162396 | SCV002532701 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-10 | criteria provided, single submitter | curation | |
Genome- |
RCV000162396 | SCV002582549 | likely benign | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000409816 | SCV002582851 | likely benign | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000409816 | SCV004017834 | benign | Li-Fraumeni syndrome 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
All of Us Research Program, |
RCV001085434 | SCV004823773 | likely benign | Li-Fraumeni syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV004017403 | SCV004848641 | likely benign | not specified | 2022-04-06 | criteria provided, single submitter | clinical testing | The p.Pro222Pro variant in TP53 is classified as likely benign because it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. It has been identified in 0.009% (11/129078) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BP4, BP7. |
Laboratory of Translational Genomics, |
RCV000119374 | SCV000154281 | not provided | Ovarian neoplasm | no assertion provided | not provided | ||
Prevention |
RCV003915186 | SCV004734901 | likely benign | TP53-related disorder | 2019-04-23 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |