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NM_000310.4(PPT1):c.3G>A (p.Met1Ile) AND Neuronal ceroid lipofuscinosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 31, 2023
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:
RCV000589397.5

Allele description [Variation Report for NM_000310.4(PPT1):c.3G>A (p.Met1Ile)]

NM_000310.4(PPT1):c.3G>A (p.Met1Ile)

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.3G>A (p.Met1Ile)
HGVS:
  • NC_000001.11:g.40097236C>T
  • NG_009192.1:g.5235G>A
  • NM_000310.4:c.3G>AMANE SELECT
  • NM_001142604.2:c.3G>A
  • NM_001363695.2:c.3G>A
  • NP_000301.1:p.Met1Ile
  • NP_000301.1:p.Met1Ile
  • NP_001136076.1:p.Met1Ile
  • NP_001350624.1:p.Met1Ile
  • LRG_690t1:c.3G>A
  • LRG_690:g.5235G>A
  • LRG_690p1:p.Met1Ile
  • NC_000001.10:g.40562908C>T
  • NM_000310.3:c.3G>A
Protein change:
M1I
Links:
dbSNP: rs386833645
NCBI 1000 Genomes Browser:
rs386833645
Molecular consequence:
  • NM_000310.4:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001142604.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001363695.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_000310.4:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001142604.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363695.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis
Synonyms:
Ceroid storage disease
Identifiers:
MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000696512Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Mar 31, 2023)
germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5.

Mole SE, Mitchison HM, Munroe PB.

Hum Mutat. 1999;14(3):199-215. Review.

PubMed [citation]
PMID:
10477428

Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

Kousi M, Lehesjoki AE, Mole SE.

Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. Review.

PubMed [citation]
PMID:
21990111
See all PubMed Citations (12)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696512.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

Variant summary: PPT1 c.3G>A (p.Met1Ile) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 247912 control chromosomes (gnomAD, v2). c.3G>A has been reported in the literature in at least three individuals affected with late-infantile or juvenile-onset Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Das_1998, Hofmann_1999). These data indicate that the variant is likely to be associated with disease. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated a greatly reduced protein expression, with a largely preserved specific activity in transfected cells, which was in accordance with the significantly reduced enzyme activity in patient derived cell lines (Das_2001, Lyly_2007, Sima_2018). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024