NM_000271.5(NPC1):c.688_693del (p.Ser230_Val231del) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Apr 28, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000271.5(NPC1):c.688_693del (p.Ser230_Val231del)]

NM_000271.5(NPC1):c.688_693del (p.Ser230_Val231del)

NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000271.5(NPC1):c.688_693del (p.Ser230_Val231del)
  • NC_000018.10:g.23560420_23560425del
  • NG_012795.1:g.31194_31199del
  • NM_000271.5:c.688_693delMANE SELECT
  • NP_000262.2:p.Ser230_Val231del
  • NC_000018.9:g.21140383_21140388del
  • NC_000018.9:g.21140384_21140389del
  • NM_000271.4:c.688_693del
  • NM_000271.4:c.688_693delTCTGTG
dbSNP: rs758687942
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000271.5:c.688_693del - inframe_deletion - [Sequence Ontology: SO:0001822]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000344636EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Aug 9, 2016)
germlineclinical testing

Citation Link,

SCV000581824GeneDxcriteria provided, single submitter
(Apr 28, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000344636.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000581824.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


The c.688_693delTCTGTG variant has been reported previously in association with Niemann-Pickdisease, type C (NPC) in patients who also harbored a second variant in the NPC1 gene (Sun et al.,2001; Imrie et al., 2015). The c.688_693delTCTGTG variant causes the loss of a Serine codon atposition 230 and the loss of a Valine codon at position 231, denoted p.Ser230_Val231. Thec.688_693delTCTGTG variant is not observed at a significant frequency in large population cohorts(Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In silico analysispredicts this variant is probably damaging to the protein structure/function. In summary, we interpretc.688_693delTCTGTG as pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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