ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.639A>G (p.Arg213=) (rs1800372)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000036533 SCV000111073 benign not specified 2015-03-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162403 SCV000212733 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: 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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000203086 SCV000257782 benign Li-Fraumeni syndrome 1 2015-07-10 criteria provided, single submitter clinical testing
Invitae RCV000206135 SCV000262407 benign Li-Fraumeni syndrome 2020-12-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000036533 SCV000305116 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000203086 SCV000407069 benign Li-Fraumeni syndrome 1 2018-01-12 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.
Counsyl RCV000203086 SCV000488466 benign Li-Fraumeni syndrome 1 2016-04-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162403 SCV000537359 benign Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282915 SCV000605419 benign none provided 2020-08-20 criteria provided, single submitter clinical testing
GeneDx RCV001572845 SCV001830120 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31748977, 30796655, 27957778, 29979965, 25896519)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036533 SCV000060188 benign not specified 2008-09-15 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000036533 SCV000692079 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000203086 SCV000733709 benign Li-Fraumeni syndrome 1 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162403 SCV000788225 likely benign Hereditary cancer-predisposing syndrome 2017-12-08 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357034 SCV001552359 benign Malignant tumor of breast no assertion criteria provided clinical testing The TP53 p.Arg213= variant was identified in 13 of 844 proband chromosomes (frequency: 0.02) from individuals or families with breast, ovarian, gastric or non-small cell lung cancer (Arcand 2015, Juvan 2007 17436385, Palacio-Rua 2014, Deben 2017). The variant was identified in dbSNP (rs1800372) as “with other allele”, ClinVar (classified as benign by Invitae, Ambry Genetics, Color and 8 other submitters; and as likely benign by Illumina and True Health Diagnostics) and LOVD 3.0 (observed 9x). The variant was identified in control databases in 3407 of 277,174 chromosomes (33 homozygous) at a frequency of 0.01, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 67 of 24,030 chromosomes (freq: 0.003), Other in 126 of 6466 chromosomes (freq: 0.02), Latino in 455 of 34,418 chromosomes (freq: 0.01), European in 2209 of 126,676 chromosomes (freq: 0.02), Ashkenazi Jewish in 343 of 10,152 chromosomes (freq: 0.03), East Asian in 2 of 18,866 chromosomes (freq: 0.0001), Finnish in 119 of 25,784 chromosomes (freq: 0.005), and South Asian in 86 of 30,782 chromosomes (freq: 0.003). The p.Arg213= variant is not expected to have clinical significance because it does not result in a change of amino acid. The variant occurs at a non-conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001572845 SCV001797847 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000036533 SCV001809091 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000036533 SCV001905939 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000036533 SCV001928843 benign not specified no assertion criteria provided clinical testing

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