Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131618 | SCV000186637 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-15 | criteria provided, single submitter | clinical testing | The c.328_339del12 variant (also known as p.R110_F113del) is located in coding exon 3 of the TP53 gene. This variant results from an in-frame deletion of 12 nucleotides (CGTCTGGGCTTC) at positions 328 to 339. This results in the in-frame deletion of 4 amino acids (RLGF) at codons 110 to 113. The amino acid positions 111 and 113 are well conserved, and amino acid positions 110 and 112 are not well conserved. Yeast-based functional assays shows that missense alterations at the deleted codons result primarily in a non-functional p53 protein (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). In addition, missense alterations in codon 110 have been identified a Li-Fraumeni family, and as germline alterations in a number of p53-related cancers, including early onset breast cancer and sarcoma (Mitchell G, PLoS ONE 2013 ; 8(7):e69026. Rath MG, Breast Cancer Res. Treat. 2013 May; 139(1):193-8. Masciari S, Genet. Med. 2011 Jul; 13(7):651-7. Rines RD, Carcinogenesis 1998 Jun; 19(6):979-84). Structural analysis indicates that this deletion exhibits structural perturbations to the DNA binding domain and would be pathogenic (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998278 | SCV005625954 | likely pathogenic | not provided | 2024-06-06 | criteria provided, single submitter | clinical testing | The TP53 c.328_339del (p.Arg110_Phe113del) variant (also known as c.328_339del12) has been reported in the published literature in at least one individual with chronic lymphocytic leukemia (PMID: 21232794 (2011)) and as a somatic variant in an individual with breast cancer (PMID: 37336919 (2023)). Other missense variants at the same codon 110 have been reported in a Li-Fraumeni family (PMID: 21552135 (2011)) and in individuals with early onset breast cancer (PMID: 23580068 (2013)) and sarcoma (PMID: 23894400 (2013)). In addition, yeast functional studies showed that missense variants at the deleted codons 110-113 result in partial loss of p53 protein function (PMID: 12826609 (2003)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic. |