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NM_001352514.2(HLCS):c.1223del (p.Gly408fs)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 27, 2020
Accession:
VCV000203777.9
Variation ID:
203777
Description:
1bp deletion
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NM_001352514.2(HLCS):c.1223del (p.Gly408fs)

Allele ID
200375
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
21q22.13
Genomic location
21: 36936663 (GRCh38) GRCh38 UCSC
21: 38308963 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000021.8:g.38308965del
NC_000021.9:g.36936665del
NM_001352514.2:c.1223del MANE Select NP_001339443.1:p.Gly408fs frameshift
... more HGVS
Protein change
G261fs, G408fs
Other names
-
Canonical SPDI
NC_000021.9:36936662:CCC:CC
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA312635
dbSNP: rs771944310
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 6 criteria provided, multiple submitters, no conflicts Aug 27, 2020 RCV000410410.8
Pathogenic 1 criteria provided, single submitter Sep 21, 2016 RCV000185969.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
HLCS - - GRCh38
GRCh37
512 578

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 21, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000238927.8
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The c.782delG deletion pathogenic variant in the HLCS gene have been reported previously in association with holocarboxylase synthetase (HLCS) deficiency (Suzuki et al., 2005). The … (more)
Pathogenic
(Apr 28, 2017)
criteria provided, single submitter
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000915952.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (4)
Comment:
The HLCS c.782delG (p.Gly261ValfsTer20) variant is a frameshift variant that is predicted to cause premature truncation of the protein. The p.Gly261ValfsTer20 variant, described as one … (more)
Pathogenic
(Sep 21, 2017)
criteria provided, single submitter
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919515.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: The HLCS c.782delG (p.Gly261ValfsX20) variant results in a premature termination codon, predicted to cause a truncated or absent HLCS protein due to nonsense … (more)
Pathogenic
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Invitae
Accession: SCV000953901.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change creates a premature translational stop signal (p.Gly261Valfs*20) in the HLCS gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Jun 07, 2017)
no assertion criteria provided
Method: curation
Holocarboxylase synthetase deficiency
Allele origin: germline
SingHealth Duke-NUS Institute of Precision Medicine
Accession: SCV000853119.1
Submitted: (Apr 09, 2018)
Evidence details
Pathogenic
(Jul 22, 2016)
no assertion criteria provided
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: unknown
Counsyl
Accession: SCV000485741.2
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (4)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001461053.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Severe neonatal holocarboxylase synthetase deficiency in west african siblings. De Castro M JIMD reports 2015 PMID: 25690727
Mutations in the holocarboxylase synthetase gene HLCS. Suzuki Y Human mutation 2005 PMID: 16134170
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. Yang X Human genetics 2001 PMID: 11735028
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. Yang X Journal of human genetics 2000 PMID: 11185745
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. Sakamoto O Journal of inherited metabolic disease 1998 PMID: 9870216
Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. Aoki Y Biochimica et biophysica acta 1995 PMID: 8541348
Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. Suzuki Y Nature genetics 1994 PMID: 7842009

Text-mined citations for rs771944310...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021