ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.63C>T (p.Asp21=) (rs1800369)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163241 SCV000213768 likely benign Hereditary cancer-predisposing syndrome 2014-06-18 criteria provided, single submitter clinical testing
Color RCV000163241 SCV000686757 likely benign Hereditary cancer-predisposing syndrome 2015-12-28 criteria provided, single submitter clinical testing
GeneDx RCV000430891 SCV000514931 benign not specified 2015-07-31 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.
Illumina Clinical Services Laboratory,Illumina RCV000196365 SCV000407075 uncertain significance Li-Fraumeni syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590622 SCV000697443 benign not provided 2017-06-23 criteria provided, single submitter clinical testing Variant summary: The TP53 c.63C>T (p.Asp21Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 73 of 119254 control chromosomes (2 homozygotes), but was observed exclusively in the South Asian subpopulation at a frequency of 0.004463 (73/16356; 2 homozygotes). This frequency is about 112 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), strongly suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant has been identified in breast cancer and lung cancer patients without evidence for pathogenicity (Holstege_Can Res_2009; Ginsburg_Fam Cancer_2009; Lee_JCMS_2010). Immunostaining studies in breast cancer tissue showed that TP53 was present in all cells analyzed, suggesting the variant does not affect expression (Holstege_Can Res_2009). Multiple clinical diagnostic laboratories/reputable databases have classified this variant with conflicting interpretations, including uncertain significance, likely benign and benign. Taken together, this variant is classified as benign.
Invitae RCV000196365 SCV000252723 benign Li-Fraumeni syndrome 2017-12-20 criteria provided, single submitter clinical testing

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