NM_000310.4(PPT1):c.86C>A (p.Pro29Gln) AND Neuronal ceroid lipofuscinosis 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 26, 2022
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:: RCV001828009.4

Allele description [Variation Report for NM_000310.4(PPT1):c.86C>A (p.Pro29Gln)]

NM_000310.4(PPT1):c.86C>A (p.Pro29Gln)

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.86C>A (p.Pro29Gln)

Other names:

p.P29Q:CCG>CAG

HGVS:

NC_000001.11:g.40097153G>T
NG_009192.1:g.5318C>A
NM_000310.4:c.86C>AMANE SELECT
NM_001142604.2:c.86C>A
NM_001363695.2:c.86C>A
NP_000301.1:p.Pro29Gln
NP_000301.1:p.Pro29Gln
NP_001136076.1:p.Pro29Gln
NP_001350624.1:p.Pro29Gln
LRG_690t1:c.86C>A
LRG_690:g.5318C>A
LRG_690p1:p.Pro29Gln
NC_000001.10:g.40562825G>T
NM_000310.3:c.86C>A

Protein change:

P29Q

Links:

dbSNP: rs778256566

NCBI 1000 Genomes Browser:

rs778256566

Molecular consequence:

NM_000310.4:c.86C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001142604.2:c.86C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363695.2:c.86C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis 1 (CLN1)
Synonyms:: CEROID LIPOFUSCINOSIS, NEURONAL, 1, VARIABLE AGE AT ONSET; CLN1 variable age at onset; Infantile CLN (type of CLN1); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009744; MedGen: C1850451; OMIM: 256730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002086011	Natera, Inc.	no assertion criteria provided	Uncertain significance (Nov 11, 2019)	germline	clinical testing
SCV003489028	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002086011

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Nov 11, 2019)

germline

clinical testing

SCV003489028

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 26, 2022)

germline

clinical testing

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Natera, Inc., SCV002086011.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003489028.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PPT1 protein function. ClinVar contains an entry for this variant (Variation ID: 206646). This variant has not been reported in the literature in individuals affected with PPT1-related conditions. This variant is present in population databases (rs778256566, gnomAD 0.009%). This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 29 of the PPT1 protein (p.Pro29Gln).

#	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

Last Updated: Sep 29, 2024

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