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NM_017882.3(CLN6):c.307C>T (p.Arg103Trp) AND Neuronal ceroid lipofuscinosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 27, 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:
RCV001051368.6

Allele description [Variation Report for NM_017882.3(CLN6):c.307C>T (p.Arg103Trp)]

NM_017882.3(CLN6):c.307C>T (p.Arg103Trp)

Gene:
CLN6:CLN6 transmembrane ER protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q23
Genomic location:
Preferred name:
NM_017882.3(CLN6):c.307C>T (p.Arg103Trp)
HGVS:
  • NC_000015.10:g.68211854G>A
  • NG_008764.2:g.50358C>T
  • NM_017882.3:c.307C>TMANE SELECT
  • NP_060352.1:p.Arg103Trp
  • LRG_832t1:c.307C>T
  • LRG_832:g.50358C>T
  • LRG_832p1:p.Arg103Trp
  • NC_000015.9:g.68504192G>A
  • NM_017882.2:c.307C>T
Protein change:
R103W
Links:
dbSNP: rs201095412
NCBI 1000 Genomes Browser:
rs201095412
Molecular consequence:
  • NM_017882.3:c.307C>T - 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
SCV001215519Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 27, 2023)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Gene symbol: CLN6. Disease: Neuronal ceroid lipofuscinosis, late Infantile.

Cismondi IA, Kohan R, Ghio A, Ramirez AM, Halac IN.

Hum Genet. 2008 Oct;124(3):324. No abstract available.

PubMed [citation]
PMID:
18846690

[Clinical, genetic and pathological features of neuronal ceroid lipofuscinosis in 5 Chinese patients].

Ren SC, Gao BQ, Wang YJ, Wu XJ, Tian ZX, Sun YL.

Zhonghua Yi Xue Za Zhi. 2016 Nov 22;96(43):3504-3507. doi: 10.3760/cma.j.issn.0376-2491.2016.43.013. Chinese.

PubMed [citation]
PMID:
27903347
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001215519.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 103 of the CLN6 protein (p.Arg103Trp). This variant is present in population databases (rs201095412, gnomAD 0.03%). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis and/or spinocerebellar ataxia (PMID: 18846690, 27903347, 31743419). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 498240). 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 CLN6 protein function with a negative predictive value of 80%. This variant disrupts the p.Arg103 amino acid residue in CLN6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21549341, 30561534). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024