ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.91G>A (p.Val31Ile) (rs201753350)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115742 SCV000187523 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Conflicting evidence
Color RCV000115742 SCV000910670 likely benign Hereditary cancer-predisposing syndrome 2016-01-14 criteria provided, single submitter clinical testing
Counsyl RCV000409871 SCV000487895 uncertain significance Li-Fraumeni syndrome 1 2015-12-10 criteria provided, single submitter clinical testing
GeneDx RCV000122173 SCV000149651 likely benign not specified 2017-10-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000122173 SCV000086388 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000123100 SCV000407074 likely benign Li-Fraumeni syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586196 SCV000697455 benign not provided 2017-04-27 criteria provided, single submitter clinical testing Variant summary: The c.91G>A (p.Val31Ile) in TP53 gene is a missense change that involves a conserved nucleotide. The variant is located just outside of the p53 transactivation domain. Although 4/5 in silico tools predict benign outcome, in the functional studies the variant displayed moderately reduced cell proliferation suppressing activity as well as transcriptional activity on p21 (CDKN1A) and MDM2 promoters, but not on the BAX promoter compared to wt-tp53 (Yamada, 2007). In addition, it is also classified as functionally competent variant in TP53 database. The variant is present in the large control population dataset of ExAC and gnomAD at a similar frequencies of 0.00026 (31/118406 and 58/275552 chromosomes tested, respectively), predominantly in individuals of East Asian descent (0.00353; 30/ 8498 chromosomes and 58/18782 chromosomes tested) including one homozygote. These frequencies exceed the maximal expected frequency of a pathogenic allele (0.000047) in this gene. The variant has been reported in several cancer-affected individuals without evidence for causality (Toguchida, 1992; Lee, 2010; Yamada, 2007; Yamaguchi, 2016) and is generally regarded as a polymorphism. In addition, one individual dx with thyroid carcinoma tested positive for BRAF V600E, further supporting benign outcome of the variant of interest. The variant was also identified in one internal LCA specimen in co-occurrence with a known pathogenic variant in MSH6 c.4068_4071dupGATT (p.K1358fs*2). Lastly, multiple reputable databases/clinical laboratories cite the variant with classification of Likely Benign. Taking all lines of evidence into consideration, this variant has been classified as Benign.
Invitae RCV000123100 SCV000166401 likely benign Li-Fraumeni syndrome 2017-12-15 criteria provided, single submitter clinical testing
Mendelics RCV000123100 SCV000839127 uncertain significance Li-Fraumeni syndrome 2018-07-02 criteria provided, single submitter clinical testing
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000409871 SCV000267534 likely pathogenic Li-Fraumeni syndrome 1 2016-03-18 criteria provided, single submitter reference population

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