Submissions for variant NM_000546.6(TP53):c.1014C>T (p.Phe338=)

gnomAD frequency: 0.00018  dbSNP: rs150293825

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213067	SCV000211784	benign	not specified	2014-07-09	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.
Ambry Genetics	RCV000161054	SCV000213005	likely benign	Hereditary cancer-predisposing syndrome	2014-07-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084218	SCV000253304	likely benign	Li-Fraumeni syndrome	2025-01-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000161054	SCV000537467	likely benign	Hereditary cancer-predisposing syndrome	2015-10-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590822	SCV000697423	benign	not provided	2016-04-25	criteria provided, single submitter	clinical testing	Variant summary: The c.1014C>T variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts damaging outcome for this variant. 5/5 splice-tools in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions are not confirmed by experimental studies. This variant is found in 26/117820 control chromosomes at a frequency of 0.0002207, which is about 6 times of the maximal expected frequency of a pathogenic allele (0.0000354), suggesting this variant is benign. In addition, multiple clinical laboratories classified this variant as benign/likely benign. Taken together, this variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000590822	SCV000806230	likely benign	not provided	2017-05-30	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000590822	SCV000889879	benign	not provided	2022-03-17	criteria provided, single submitter	clinical testing
Mendelics	RCV000989699	SCV001140238	likely benign	Squamous cell carcinoma of the head and neck	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590822	SCV001151189	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	TP53: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001127283	SCV001286578	likely benign	Li-Fraumeni syndrome 1	2019-11-18	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Sema4, Sema4	RCV000161054	SCV002530418	benign	Hereditary cancer-predisposing syndrome	2021-04-20	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000161054	SCV002582214	likely benign	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001127283	SCV002582776	likely benign	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000213067	SCV002760879	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590822	SCV003799832	likely benign	not provided	2024-03-21	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001127283	SCV004015639	benign	Li-Fraumeni syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001084218	SCV004823729	likely benign	Li-Fraumeni syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000213067	SCV000692059	likely benign	not specified		no assertion criteria provided	clinical testing