NM_000546.6(TP53):c.1000G>C (p.Gly334Arg) AND Li-Fraumeni syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 11, 2023
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:: RCV000663214.5

Allele description [Variation Report for NM_000546.6(TP53):c.1000G>C (p.Gly334Arg)]

NM_000546.6(TP53):c.1000G>C (p.Gly334Arg)

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.1000G>C (p.Gly334Arg)

Other names:

p.G334R:GGG>CGG

HGVS:

NC_000017.11:g.7670709C>G
NG_017013.2:g.21842G>C
NM_000546.6:c.1000G>CMANE SELECT
NM_001126112.3:c.1000G>C
NM_001126113.3:c.*19G>C
NM_001126114.3:c.*107G>C
NM_001126115.2:c.604G>C
NM_001126116.2:c.*107G>C
NM_001126117.2:c.*19G>C
NM_001126118.2:c.883G>C
NM_001276695.3:c.*19G>C
NM_001276696.3:c.*107G>C
NM_001276697.3:c.523G>C
NM_001276698.3:c.*107G>C
NM_001276699.3:c.*19G>C
NM_001276760.3:c.883G>C
NM_001276761.3:c.883G>C
NP_000537.3:p.Gly334Arg
NP_000537.3:p.Gly334Arg
NP_001119584.1:p.Gly334Arg
NP_001119587.1:p.Gly202Arg
NP_001119590.1:p.Gly295Arg
NP_001263626.1:p.Gly175Arg
NP_001263689.1:p.Gly295Arg
NP_001263690.1:p.Gly295Arg
LRG_321t1:c.1000G>C
LRG_321t6:c.*107G>C
LRG_321:g.21842G>C
LRG_321p1:p.Gly334Arg
NC_000017.10:g.7574027C>G
NM_000546.4:c.1000G>C
NM_000546.5(TP53):c.1000G>C
NM_000546.5:c.1000G>C
NM_001126116.1:c.*107G>C
p.G334R
p.Gly334Arg

Protein change:

G175R

Links:

dbSNP: rs730882028

NCBI 1000 Genomes Browser:

rs730882028

Molecular consequence:

NM_001126113.3:c.*19G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126114.3:c.*107G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126116.2:c.*107G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126117.2:c.*19G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276695.3:c.*19G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276696.3:c.*107G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276698.3:c.*107G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276699.3:c.*19G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000546.6:c.1000G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.1000G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.604G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.883G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.523G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.883G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.883G>C - 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
SCV000786400	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Apr 25, 2018)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24448499, 25584008, 23580068, 25503501 Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV004017857	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Apr 11, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25584008, 32675277 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000786400

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(Apr 25, 2018)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf,

Citation Link,

SCV004017857

Myriad Genetics, Inc.

criteria provided, single submitter

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

Likely pathogenic
(Apr 11, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Integrated analysis of germline and somatic variants in ovarian cancer.

Kanchi KL, Johnson KJ, Lu C, McLellan MD, Leiserson MD, Wendl MC, Zhang Q, Koboldt DC, Xie M, Kandoth C, McMichael JF, Wyczalkowski MA, Larson DE, Schmidt HK, Miller CA, Fulton RS, Spellman PT, Mardis ER, Druley TE, Graubert TA, Goodfellow PJ, Raphael BJ, et al.

Nat Commun. 2014;5:3156. doi: 10.1038/ncomms4156.

PubMed [citation]

PMID:: 24448499
PMCID:: PMC4025965

Prevalence of germline TP53 mutations in HER2+ breast cancer patients.

Rath MG, Masciari S, Gelman R, Miron A, Miron P, Foley K, Richardson AL, Krop IE, Verselis SJ, Dillon DA, Garber JE.

Breast Cancer Res Treat. 2013 May;139(1):193-8. doi: 10.1007/s10549-012-2375-z. Epub 2013 Apr 12.

PubMed [citation]

PMID:: 23580068
PMCID:: PMC4280061

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000786400.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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

From Myriad Genetics, Inc., SCV004017857.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 25584008, 32675277]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 25584008, 32675277].

#	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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