NM_000546.6(TP53):c.388C>T (p.Leu130Phe) AND Li-Fraumeni syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 13, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002288816.3

Allele description [Variation Report for NM_000546.6(TP53):c.388C>T (p.Leu130Phe)]

NM_000546.6(TP53):c.388C>T (p.Leu130Phe)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.388C>T (p.Leu130Phe)

HGVS:

NC_000017.11:g.7675224G>A
NG_017013.2:g.17327C>T
NM_000546.6:c.388C>TMANE SELECT
NM_001126112.3:c.388C>T
NM_001126113.3:c.388C>T
NM_001126114.3:c.388C>T
NM_001126115.2:c.-9C>T
NM_001126116.2:c.-9C>T
NM_001126117.2:c.-9C>T
NM_001126118.2:c.271C>T
NM_001276695.3:c.271C>T
NM_001276696.3:c.271C>T
NM_001276697.3:c.-90C>T
NM_001276698.3:c.-90C>T
NM_001276699.3:c.-90C>T
NM_001276760.3:c.271C>T
NM_001276761.3:c.271C>T
NP_000537.3:p.Leu130Phe
NP_000537.3:p.Leu130Phe
NP_001119584.1:p.Leu130Phe
NP_001119585.1:p.Leu130Phe
NP_001119586.1:p.Leu130Phe
NP_001119590.1:p.Leu91Phe
NP_001263624.1:p.Leu91Phe
NP_001263625.1:p.Leu91Phe
NP_001263689.1:p.Leu91Phe
NP_001263690.1:p.Leu91Phe
LRG_321t1:c.388C>T
LRG_321:g.17327C>T
LRG_321p1:p.Leu130Phe
NC_000017.10:g.7578542G>A
NM_000546.4:c.388C>T
NM_000546.5:c.388C>T
P04637:p.Leu130Phe

Protein change:

L130F

Links:

UniProtKB: P04637#VAR_044730; dbSNP: rs863224683

NCBI 1000 Genomes Browser:

rs863224683

Molecular consequence:

NM_001126115.2:c.-9C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.2:c.-9C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.2:c.-9C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.3:c.-90C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-90C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-90C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.271C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002582657	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004933139	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Feb 13, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002582657

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004933139

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Feb 13, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]

PMID:: 29979965

Details of each submission

From Genome-Nilou Lab, SCV002582657.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004933139.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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