NM_001352514.2(HLCS):c.1096dup (p.Ile366fs) AND Holocarboxylase synthetase deficiency

Clinical significance:Pathogenic (Last evaluated: Dec 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000001990.6

Allele description [Variation Report for NM_001352514.2(HLCS):c.1096dup (p.Ile366fs)]

NM_001352514.2(HLCS):c.1096dup (p.Ile366fs)

Gene:
HLCS:holocarboxylase synthetase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
21q22.13
Genomic location:
Preferred name:
NM_001352514.2(HLCS):c.1096dup (p.Ile366fs)
HGVS:
  • NC_000021.9:g.36936790dup
  • NG_016193.2:g.58605dup
  • NM_000411.8:c.655dup
  • NM_001242784.3:c.655dup
  • NM_001242785.2:c.655dup
  • NM_001352514.2:c.1096dupMANE SELECT
  • NM_001352515.2:c.655dup
  • NM_001352516.2:c.655dup
  • NM_001352517.1:c.655dup
  • NM_001352518.1:c.655dup
  • NP_000402.3:p.Ile219fs
  • NP_001229713.1:p.Ile219fs
  • NP_001229714.1:p.Ile219fs
  • NP_001339443.1:p.Ile366fs
  • NP_001339444.1:p.Ile219fs
  • NP_001339445.1:p.Ile219fs
  • NP_001339446.1:p.Ile219fs
  • NP_001339447.1:p.Ile219fs
  • NC_000021.8:g.38309089_38309090insT
  • NC_000021.8:g.38309090dup
  • NM_000411.6:c.655dup
  • NM_000411.6:c.655dupA
  • NR_148020.2:n.955dup
  • NR_148021.1:n.1112dup
Protein change:
I219fs
Links:
OMIM: 609018.0008; dbSNP: rs773102942
NCBI 1000 Genomes Browser:
rs773102942
Molecular consequence:
  • NM_000411.8:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001242784.3:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001242785.2:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352514.2:c.1096dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352515.2:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352516.2:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352517.1:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352518.1:c.655dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_148020.2:n.955dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148021.1:n.1112dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Holocarboxylase synthetase deficiency
Synonyms:
MULTIPLE CARBOXYLASE DEFICIENCY, EARLY ONSET
Identifiers:
MONDO: MONDO:0009666; MedGen: C0268581; Orphanet: 79242; OMIM: 253270

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000022148OMIMno assertion criteria providedPathogenic
(Nov 1, 2001)
germlineliterature only

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

SCV000949301Invitaecriteria provided, single submitter
Pathogenic
(Dec 17, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency.

Yang X, Aoki Y, Li X, Sakamoto O, Hiratsuka M, Kure S, Taheri S, Christensen E, Inui K, Kubota M, Ohira M, Ohki M, Kudoh J, Kawasaki K, Shibuya K, Shintani A, Asakawa S, Minoshima S, Shimizu N, Narisawa K, Matsubara Y, Suzuki Y.

Hum Genet. 2001 Nov;109(5):526-34. Epub 2001 Oct 5.

PubMed [citation]
PMID:
11735028

Mutations in the holocarboxylase synthetase gene HLCS.

Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y.

Hum Mutat. 2005 Oct;26(4):285-90. Review.

PubMed [citation]
PMID:
16134170
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000022148.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a large survey of HLCS mutations in Japanese patients with biotin-responsive multiple carboxylase deficiency (253270), Yang et al. (2001) identified a 1-bp insertion (655_656insA) in the HLCS gene.

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

From Invitae, SCV000949301.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Ile219Asnfs*58) in the HLCS gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs773102942, ExAC 0.03%). This variant has been observed in individuals affected with holocarboxylase synthetase deficiency (PMID: 11735028). This variant is also known as 655–656insA in the literature. ClinVar contains an entry for this variant (Variation ID: 1913). Loss-of-function variants in HLCS are known to be pathogenic (PMID: 16134170). 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: Oct 7, 2021

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