ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.108G>A (p.Pro36=) (rs1800370)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119149 SCV000153868 benign Li-Fraumeni syndrome 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162410 SCV000212746 benign Hereditary cancer-predisposing syndrome 2014-12-17 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Synonymous alterations with insufficient evidence to classify as benign
PreventionGenetics,PreventionGenetics RCV000244898 SCV000305113 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000611879 SCV000407072 benign Li-Fraumeni syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Health, Inc RCV000162410 SCV000537364 benign Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000244898 SCV000884713 benign not specified 2018-07-13 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000244898 SCV000692097 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000611879 SCV000733711 benign Li-Fraumeni syndrome 1 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162410 SCV000788223 likely benign Hereditary cancer-predisposing syndrome 2018-02-20 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358051 SCV001553694 benign Malignant tumor of breast no assertion criteria provided clinical testing The TP53 p.Pro36= variant was identified in 4 of 152 proband chromosomes (frequency: 0.03) from French Canadian and Brazilian individuals or families with hereditary breast and ovarian cancers or Li-Fraumeni like syndrome (Arcand 2015, Palmero 2016). The variant was also identified in 3 of 28 gastric tumours, either individually or in combination with the TP53 P72R polymorphism (Juvan 2007); and in 1 of 101 sporadic CRC tumours (Lopez 2012). The variant was identified in ClinVar (classified benign by Invitae, Ambry Genetics, Prevention Genetics and Color Genomics Inc., and likely benign by Illumina), Clinvitae (classifications benign and conflicting interpretations of pathogenicity) and the IARC TP53 Database (as a validated polymorphism). The variant was not identified in Genesight-COGR, Cosmic, LOVD 3.0, UMD TP52 Mutation Database (not available), and Database of germline p53 mutations. The variant was identified in control databases in 3520 (38 homozygous) of 277012 chromosomes at a frequency of 0.013 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: Latino in 1043 of 34398 chromosomes (freq: 0.03), European (Non-Finnish) in 1769 of 126630 chromosomes (freq: 0.014), Other in 77 of 6456 chromosomes (freq: 0.012), and South Asian in 331 of 30778 chromosomes (freq: 0.011). The p.Pro36Pro variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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