ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.85_87AAC[1] (p.Asn30del) (rs587782270)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131064 SCV000185994 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000131064 SCV000691661 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-09 criteria provided, single submitter clinical testing
GeneDx RCV000656986 SCV000211786 uncertain significance not provided 2017-08-18 criteria provided, single submitter clinical testing This in-frame deletion of 3 nucleotides in TP53 is denoted c.88_90delAAC at the cDNA level and p.Asn30del (N30del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAAC[delAAC]GTTC. This deletion of a single Asparagine residue occurs at a position that is not conserved and is located in the transactivation domain (Bode 2004, Pessoa 2014). This variant was observed in an individual undergoing clinical testing for hereditary cancer (Chong 2014). TP53 c.88_90delAAC was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). In silico analyses predict that this variant is unlikely to alter protein structure or function. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider TP53 c.88_90delAAC to be a variant of uncertain significance.
Invitae RCV000227012 SCV000285216 uncertain significance Li-Fraumeni syndrome 2018-09-28 criteria provided, single submitter clinical testing This variant, c.88_90delAAC, results in the deletion of 1 amino acid of the TP53 protein (p.Asn30del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587782270, ExAC 0.01%). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 142158). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000213045 SCV000712881 uncertain significance not specified 2017-03-09 criteria provided, single submitter clinical testing The p.Asn30del variant in TP53 has been reported as a germline variant in 1 indi vidual who underwent clinical testing for hereditary cancer, who also carried a pathogenic variant in the BRCA2 gene (Chong 2014), and has also been reported in ClinVar (Variation ID 142158). It has also been identified in 1/64924 of Europe an chromosomes and 1/9660 of African chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs587782270). This variant is a deletion of 1 amino acid at position 30 and is not predicted to alter the prot ein reading-frame. It is unclear if this deletion will impact the protein. In su mmary, the clinical significance of the p.Asn30del variant is uncertain.

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