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NM_000310.4(PPT1):c.721del (p.Ser241fs) AND Neuronal ceroid lipofuscinosis 1

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Jan 22, 2021
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:
RCV000673437.7

Allele description [Variation Report for NM_000310.4(PPT1):c.721del (p.Ser241fs)]

NM_000310.4(PPT1):c.721del (p.Ser241fs)

Gene:
PPT1:palmitoyl-protein thioesterase 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.2
Genomic location:
Preferred name:
NM_000310.4(PPT1):c.721del (p.Ser241fs)
HGVS:
  • NC_000001.11:g.40078566del
  • NG_009192.1:g.23906del
  • NM_000310.4:c.721delMANE SELECT
  • NM_001142604.2:c.412del
  • NM_001363695.2:c.721del
  • NP_000301.1:p.Ser241fs
  • NP_001136076.1:p.Ser138fs
  • NP_001350624.1:p.Ser241fs
  • LRG_690:g.23906del
  • NC_000001.10:g.40544237del
  • NC_000001.10:g.40544238del
  • NM_000310.3:c.721delT
Protein change:
S138fs
Links:
dbSNP: rs1553166499
NCBI 1000 Genomes Browser:
rs1553166499
Molecular consequence:
  • NM_000310.4:c.721del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001142604.2:c.412del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001363695.2:c.721del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000798639Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))
Likely pathogenic
(Mar 16, 2018)
unknownclinical testing

Citation Link,

SCV001592245Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 22, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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 Counsyl, SCV000798639.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001592245.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the PPT1 protein. Other variant(s) that disrupt this region (p.Asp267Thrfs*5) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with PPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 557311). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the PPT1 gene (p.Ser241Argfs*31). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acids of the PPT1 protein.

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

Last Updated: Mar 5, 2024