NM_000391.4(TPP1):c.1435C>G (p.Pro479Ala) AND Neuronal ceroid lipofuscinosis 2

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 28, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001829780.9

Allele description [Variation Report for NM_000391.4(TPP1):c.1435C>G (p.Pro479Ala)]

NM_000391.4(TPP1):c.1435C>G (p.Pro479Ala)

Gene:

TPP1:tripeptidyl peptidase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000391.4(TPP1):c.1435C>G (p.Pro479Ala)

HGVS:

NC_000011.10:g.6614982G>C
NG_008653.1:g.9480C>G
NM_000391.4:c.1435C>GMANE SELECT
NP_000382.3:p.Pro479Ala
LRG_830t1:c.1435C>G
LRG_830:g.9480C>G
LRG_830p1:p.Pro479Ala
NC_000011.9:g.6636213G>C
NM_000391.3:c.1435C>G

Protein change:

P479A

Links:

dbSNP: rs756530648

NCBI 1000 Genomes Browser:

rs756530648

Molecular consequence:

NM_000391.4:c.1435C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis 2
Synonyms:: JANSKY-BIELSCHOWSKY DISEASE NEURONAL CEROID LIPOFUSCINOSIS, LATE INFANTILE; TPP1-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:: MONDO: MONDO:0008769; MedGen: C1876161; Orphanet: 168491; Orphanet: 228349; Orphanet: 79264; OMIM: 204500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002094805	Natera, Inc.	no assertion criteria provided	Uncertain significance (Nov 11, 2019)	germline	clinical testing
SCV004708149	Human Genetics Section, Sidra Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 28, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002094805

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Nov 11, 2019)

germline

clinical testing

SCV004708149

Human Genetics Section, Sidra Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 28, 2024)

germline

research

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

Help

Summary from all submissions

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

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

Details of each submission

From Natera, Inc., SCV002094805.1

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

#	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 Human Genetics Section, Sidra Medicine, SCV004708149.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	South Asian	1	not provided	not provided	research	PubMed (1)

Description

computational prediction tools unanimously support a deleterious effect on the gene. Extremely low frequency in GnomAD ( Total allele frequency in GnomAD 0.00001193). The variant is classified as likely pathogenic according to ACMG criteria.

#	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		1	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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