NM_000310.4(PPT1):c.665T>C (p.Leu222Pro) AND Neuronal ceroid lipofuscinosis

Clinical significance:Pathogenic (Last evaluated: Nov 1, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001192781.1

Allele description [Variation Report for NM_000310.4(PPT1):c.665T>C (p.Leu222Pro)]

NM_000310.4(PPT1):c.665T>C (p.Leu222Pro)

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.665T>C (p.Leu222Pro)
HGVS:
  • NC_000001.11:g.40078621A>G
  • NG_009192.1:g.23850T>C
  • NM_000310.4:c.665T>CMANE SELECT
  • NM_001142604.2:c.356T>C
  • NM_001363695.2:c.665T>C
  • NP_000301.1:p.Leu222Pro
  • NP_000301.1:p.Leu222Pro
  • NP_001136076.1:p.Leu119Pro
  • NP_001350624.1:p.Leu222Pro
  • LRG_690t1:c.665T>C
  • LRG_690:g.23850T>C
  • LRG_690p1:p.Leu222Pro
  • NC_000001.10:g.40544293A>G
  • NM_000310.3:c.665T>C
  • P50897:p.Leu222Pro
Protein change:
L119P
Links:
UniProtKB: P50897#VAR_066879; dbSNP: rs386833661
NCBI 1000 Genomes Browser:
rs386833661
Molecular consequence:
  • NM_000310.4:c.665T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001142604.2:c.356T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363695.2:c.665T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis
Synonyms:
Ceroid storage disease; Lipofuscin 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
SCV001361119Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Nov 1, 2019)
germlineclinical testing

PubMed (5)
[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 epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy.

Santorelli FM, Garavaglia B, Cardona F, Nardocci N, Bernardina BD, Sartori S, Suppiej A, Bertini E, Claps D, Battini R, Biancheri R, Filocamo M, Pezzini F, Simonati A.

Orphanet J Rare Dis. 2013 Feb 2;8:19. doi: 10.1186/1750-1172-8-19.

PubMed [citation]
PMID:
23374165
PMCID:
PMC3570295

Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations.

Simonati A, Tessa A, Bernardina BD, Biancheri R, Veneselli E, Tozzi G, Bonsignore M, Grosso S, Piemonte F, Santorelli FM.

Pediatr Neurol. 2009 Apr;40(4):271-6. doi: 10.1016/j.pediatrneurol.2008.10.018.

PubMed [citation]
PMID:
19302939
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361119.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: PPT1 c.665T>C (p.Leu222Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 31368 control chromosomes. c.665T>C has been reported in the literature in multiple individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Mazzei_2002, Simonati_2009, Santorelli_2013). These data indicate that the variant is very likely to be associated with disease. Simonati et al report that this mutation occurs in the hydrophobic pouch of PPT-1, and the introduction of a proline may hamper the correct folding and therefore the beta-sheet conformation of the protein (Simonati_2009). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. 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: Jan 12, 2022

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