NM_000310.4(PPT1):c.674T>C (p.Phe225Ser) AND not provided

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Jul 1, 2024
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:: RCV003328554.13

Allele description [Variation Report for NM_000310.4(PPT1):c.674T>C (p.Phe225Ser)]

NM_000310.4(PPT1):c.674T>C (p.Phe225Ser)

Gene:

PPT1:palmitoyl-protein thioesterase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_000310.4(PPT1):c.674T>C (p.Phe225Ser)

Other names:

p.Phe225Ser

HGVS:

NC_000001.11:g.40078612A>G
NG_009192.1:g.23859T>C
NM_000310.4:c.674T>CMANE SELECT
NM_001142604.2:c.365T>C
NM_001363695.2:c.674T>C
NP_000301.1:p.Phe225Ser
NP_000301.1:p.Phe225Ser
NP_001136076.1:p.Phe122Ser
NP_001350624.1:p.Phe225Ser
LRG_690t1:c.674T>C
LRG_690:g.23859T>C
LRG_690p1:p.Phe225Ser
NC_000001.10:g.40544284A>G
NM_000310.3:c.674T>C

Protein change:

F122S

Links:

dbSNP: rs386833662

NCBI 1000 Genomes Browser:

rs386833662

Molecular consequence:

NM_000310.4:c.674T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001142604.2:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363695.2:c.674T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004035749	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 13, 2023)	germline	clinical testing	Citation Link,
SCV004704131	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Jul 1, 2024)	germline	clinical testing	Citation Link,
SCV005413530	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 6, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 10781062, 11589007, 11589012, 12125808, 14997939, 15965709, 21990111, 31741823, 34695666, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004035749

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Mar 13, 2023)

germline

clinical testing

Citation Link,

SCV004704131

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Jul 1, 2024)

germline

clinical testing

Citation Link,

SCV005413530

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 6, 2023)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis.

Bellizzi JJ 3rd, Widom J, Kemp C, Lu JY, Das AK, Hofmann SL, Clardy J.

Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4573-8.

PubMed [citation]

PMID:: 10781062
PMCID:: PMC18274

Infantile neuronal ceroid lipofuscinosis: no longer just a 'Finnish' disease.

Hofmann SL, Das AK, Lu JY, Wisniewski KE, Gupta P.

Eur J Paediatr Neurol. 2001;5 Suppl A:47-51.

PubMed [citation]

PMID:: 11589007

See all PubMed Citations (10)

Details of each submission

From GeneDx, SCV004035749.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11589007, 11589012, 12125808, 14997939, 31741823, 34695666, Sangeeth_2019_Poster)

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV004704131.11

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

Description

PPT1: PM3:Strong, PM1, PM2, PP3

#	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		3	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV005413530.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (10)

Description

PP3, PP4, PM2_moderate, PM3, PS4_moderate

#	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		1	not provided	not provided	not provided

Last Updated: Apr 20, 2025

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