NM_006493.4(CLN5):c.188G>C (p.Arg63Pro) AND Neuronal ceroid lipofuscinosis

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Aug 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000989149.2

Allele description [Variation Report for NM_006493.4(CLN5):c.188G>C (p.Arg63Pro)]

NM_006493.4(CLN5):c.188G>C (p.Arg63Pro)

Genes:
CLN5:CLN5 intracellular trafficking protein [Gene - OMIM - HGNC]
FBXL3:F-box and leucine rich repeat protein 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q22.3
Genomic location:
Preferred name:
NM_006493.4(CLN5):c.188G>C (p.Arg63Pro)
HGVS:
  • NC_000013.11:g.76995077G>C
  • NG_009064.1:g.8154G>C
  • NM_001366624.2:c.188G>C
  • NM_006493.4:c.188G>CMANE SELECT
  • NP_001353553.1:p.Arg63Pro
  • NP_006484.2:p.Arg63Pro
  • LRG_692t1:c.335G>C
  • LRG_692:g.8154G>C
  • NC_000013.10:g.77569212G>C
  • NM_006493.2:c.335G>C
Protein change:
R63P
Links:
dbSNP: rs104894386
NCBI 1000 Genomes Browser:
rs104894386
Molecular consequence:
  • NM_001366624.2:c.188G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006493.4:c.188G>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
SCV001139365Mendelicscriteria provided, single submitter
Pathogenic
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001494463Invitaecriteria provided, single submitter
Uncertain significance
(Aug 15, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency.

Bessa C, Teixeira CA, Mangas M, Dias A, Sá Miranda MC, Guimarães A, Ferreira JC, Canas N, Cabral P, Ribeiro MG.

Mol Genet Metab. 2006 Nov;89(3):245-53. Epub 2006 Jun 30.

PubMed [citation]
PMID:
16814585

A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset.

Pineda-Trujillo N, Cornejo W, Carrizosa J, Wheeler RB, Múnera S, Valencia A, Agudelo-Arango J, Cogollo A, Anderson G, Bedoya G, Mole SE, Ruíz-Linares A.

Neurology. 2005 Feb 22;64(4):740-2.

PubMed [citation]
PMID:
15728307
See all PubMed Citations (5)

Details of each submission

From Mendelics, SCV001139365.1

#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, SCV001494463.1

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

Description

This sequence change replaces arginine with proline at codon 112 of the CLN5 protein (p.Arg112Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 16814585). ClinVar contains an entry for this variant (Variation ID: 56533). Experimental studies have shown that this variant affects CLN5 protein function (PMID: 20052765). This variant disrupts the p.Arg112 amino acid residue in CLN5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15728307, 20052765, 30078242). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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

Last Updated: Jan 12, 2022

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