Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000815181 | SCV000955628 | pathogenic | Li-Fraumeni syndrome | 2019-11-12 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with glutamine at codon 179 of the TP53 protein (p.His179Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast cancer or acute myeloid leukemia (PMID: 28724667, 26230955). ClinVar contains an entry for this variant (Variation ID: 376607). Experimental studies have shown that this missense change results in defective TP53 transactivation activity and severely attenuated cell-cycle checkpoint function (PMID: 12826609, 17311302, 16209708, 22540896). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant (c.537T>A) giving rise to the same protein effect observed here (p.His179Gln) has been determined to be pathogenic (PMID: 19556618). This suggests that this variant is also likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
Database of Curated Mutations |
RCV000444951 | SCV000508371 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421558 | SCV000508372 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431364 | SCV000508373 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444976 | SCV000508374 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425896 | SCV000508375 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436580 | SCV000508376 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444017 | SCV000508377 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425641 | SCV000508378 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437195 | SCV000508379 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419975 | SCV000508380 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429821 | SCV000508381 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436952 | SCV000508382 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420594 | SCV000508383 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431267 | SCV000508384 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441082 | SCV000508385 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423857 | SCV000508386 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428479 | SCV000508387 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439103 | SCV000508388 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421045 | SCV000508389 | likely pathogenic | Carcinoma of gallbladder | 2016-05-31 | no assertion criteria provided | literature only |