ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.482_487del (p.Ala161_Tyr163delinsAsp)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel,ClinGen RCV001250514 SCV001481785 uncertain significance Li-Fraumeni syndrome 1 2021-02-22 reviewed by expert panel curation This variant has been reported in 1 proband meeting Classic LFS criteria (PS4_Supporting; internal clinical contributor). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). There are 2 TP53 pathogenic variants (p.Y163C, p.A161D) previously reported at this codon (PM5; ClinVar ID 127814, 422295). In summary, the clinical significance of TP53 c.482_487del (p.Ala161_Tyr163delinsAsp) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM5, PM2_Supporting, PS4_Supporting.
Johns Hopkins Genomics, Johns Hopkins University RCV001250514 SCV001425306 likely pathogenic Li-Fraumeni syndrome 1 2020-03-06 criteria provided, single submitter clinical testing
Invitae RCV001361575 SCV001557553 uncertain significance Li-Fraumeni syndrome 2020-02-26 criteria provided, single submitter clinical testing This variant, c.482_487del, results in the deletion of 2 amino acid(s) of the TP53 protein (p.Ala161_Tyr163delinsAsp), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Tyr163 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8164043, 18685109, 19556618, 12826609, 16861262). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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