ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.754_762del (p.Leu252_Ile254del)

dbSNP: rs2073243450
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001046315 SCV001210212 pathogenic Li-Fraumeni syndrome 2023-07-17 criteria provided, single submitter clinical testing This variant, c.754_762del, results in the deletion of 3 amino acid(s) of the TP53 protein (p.Leu252_Ile254del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 843641). This variant disrupts a region of the TP53 protein in which other variant(s) (p.Ile254Asn) have been determined to be pathogenic (PMID: 17724467, 29070607). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002393228 SCV002672046 likely pathogenic Hereditary cancer-predisposing syndrome 2021-03-09 criteria provided, single submitter clinical testing The c.754_762delCTCACCATC variant (also known as p.L252_I254del) is located in coding exon 6 of the TP53 gene. This variant results from an in-frame CTCACCATC deletion at nucleotide positions 754 to 762, and a deletion of 3 amino acids from 252 to 254. This amino acid region is well conserved in available vertebrate species. This alteration was identified in a patient with TP53 related tumors (Bougeard G et al. J Med Genet, 2008 Aug;45:535-8). Based on internal structural analysis, L252_I254del disrupts the sensitive DNA-binding domain of TP53 to a higher degree than nearby pathogenic variants (Golovenko D et al. Structure, 2018 09;26:1237-1250.e6). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Myriad Genetics, Inc. RCV004031432 SCV004931480 likely pathogenic Li-Fraumeni syndrome 1 2024-02-16 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].

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