NM_138711.6(PPARG):c.362A>G (p.Tyr121Cys) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 17, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001382404.11

Allele description [Variation Report for NM_138711.6(PPARG):c.362A>G (p.Tyr121Cys)]

NM_138711.6(PPARG):c.362A>G (p.Tyr121Cys)

Gene:

PPARG:peroxisome proliferator activated receptor gamma [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.2

Genomic location:

Preferred name:

NM_138711.6(PPARG):c.362A>G (p.Tyr121Cys)

HGVS:

NC_000003.12:g.12381463A>G
NG_011749.1:g.98614A>G
NM_001330615.4:c.362A>G
NM_001354666.3:c.362A>G
NM_001354667.3:c.362A>G
NM_001354668.2:c.452A>G
NM_001354669.2:c.-66A>G
NM_001354670.2:c.368A>G
NM_001374261.3:c.362A>G
NM_001374262.3:c.362A>G
NM_001374263.2:c.362A>G
NM_001374264.2:c.362A>G
NM_001374265.1:c.452A>G
NM_001374266.1:c.368A>G
NM_005037.7:c.362A>G
NM_015869.5:c.452A>G
NM_138711.6:c.362A>GMANE SELECT
NM_138712.5:c.362A>G
NP_001317544.2:p.Tyr121Cys
NP_001341595.2:p.Tyr121Cys
NP_001341596.2:p.Tyr121Cys
NP_001341597.1:p.Tyr151Cys
NP_001341599.1:p.Tyr123Cys
NP_001361190.2:p.Tyr121Cys
NP_001361191.2:p.Tyr121Cys
NP_001361192.2:p.Tyr121Cys
NP_001361193.2:p.Tyr121Cys
NP_001361194.1:p.Tyr151Cys
NP_001361195.1:p.Tyr123Cys
NP_005028.5:p.Tyr121Cys
NP_056953.2:p.Tyr151Cys
NP_619725.3:p.Tyr121Cys
NP_619726.3:p.Tyr121Cys
NC_000003.11:g.12422962A>G
NM_015869.4:c.452A>G

Protein change:

Y121C

Links:

dbSNP: rs1354592503

NCBI 1000 Genomes Browser:

rs1354592503

Molecular consequence:

NM_001354669.2:c.-66A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001330615.4:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354666.3:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354667.3:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354668.2:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354670.2:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374261.3:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374262.3:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374263.2:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374264.2:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374265.1:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374266.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005037.7:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015869.5:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_138711.6:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_138712.5:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001581157	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21479595, 28641778, 28492532
SCV001765776	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jan 17, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581157

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 5, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001765776

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Jan 17, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterisation of non-obese diabetic patients with marked insulin resistance identifies a novel familial partial lipodystrophy-associated PPARγ mutation (Y151C).

Visser ME, Kropman E, Kranendonk ME, Koppen A, Hamers N, Stroes ES, Kalkhoven E, Monajemi H.

Diabetologia. 2011 Jul;54(7):1639-44. doi: 10.1007/s00125-011-2142-4. Epub 2011 Apr 9.

PubMed [citation]

PMID:: 21479595
PMCID:: PMC3110271

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy.

Akinci B, Onay H, Demir T, Savas-Erdeve Ş, Gen R, Simsir IY, Keskin FE, Erturk MS, Uzum AK, Yaylali GF, Ozdemir NK, Atik T, Ozen S, Yurekli BS, Apaydin T, Altay C, Akinci G, Demir L, Comlekci A, Secil M, Oral EA.

Metabolism. 2017 Jul;72:109-119. doi: 10.1016/j.metabol.2017.04.010. Epub 2017 Apr 27.

PubMed [citation]

PMID:: 28641778

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581157.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces tyrosine with cysteine at codon 151 of the PPARG protein (p.Tyr151Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects PPARG protein function (PMID: 21479595). This variant has been observed in individual(s) with familial partial lipodystrophy (PMID: 21479595, 28641778). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency).

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

From GeneDx, SCV001765776.3

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

Description

Published functional studies demonstrate loss-of-function with reduced DNA binding and reduced transcriptional activity (Visser et al., 2011; Majithia et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25157153, 21479595, 28641778, 32041611, 34670072, 33832869)

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

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine