In-frame deletion of one amino acid in a non-repeat region; Commonly identified and reported variant in patients with CDG-Ic (Hanefeld et al., 2000; Sun et al., 2005; Morava et al., 2006); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10924277, 21811164, 10832578, 12855228, 16007612, 27287710, 27535533)
ClinVar Genomic variation as it relates to human health
NM_013339.4(ALG6):c.894AAT[1] (p.Ile299del)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(8)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_013339.4(ALG6):c.894AAT[1] (p.Ile299del)
Variation ID: 30420 Accession: VCV000030420.16
- Type and length
-
Microsatellite, 3 bp
- Location
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Cytogenetic: 1p31.3 1: 63414137-63414139 (GRCh38) [ NCBI UCSC ] 1: 63879808-63879810 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 21, 2017 Jun 17, 2024 Feb 10, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_013339.4:c.894AAT[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_037471.2:p.Ile299del inframe deletion NM_013339.4:c.897_899del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000001.11:g.63414138AAT[1] NC_000001.10:g.63879809AAT[1] NG_008925.2:g.51549AAT[1] NG_008925.2:g.51552_51554del LRG_1260:g.51549AAT[1] LRG_1260t1:c.894AAT[1] LRG_1260p1:p.Ile299del - Protein change
- I299del
- Other names
- -
- Canonical SPDI
- NC_000001.11:63414136:TAATAAT:TAAT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| ALG6 | - | - |
GRCh38 GRCh37 |
771 | 805 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 10, 2024 | RCV000023373.20 | |
| Likely pathogenic (4) |
criteria provided, single submitter
|
Feb 21, 2022 | RCV001529107.14 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Feb 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002099588.2
First in ClinVar: Mar 05, 2022 Last updated: Mar 04, 2023 |
Comment:
In-frame deletion of one amino acid in a non-repeat region; Commonly identified and reported variant in patients with CDG-Ic (Hanefeld et al., 2000; Sun et … (more)
In-frame deletion of one amino acid in a non-repeat region; Commonly identified and reported variant in patients with CDG-Ic (Hanefeld et al., 2000; Sun et al., 2005; Morava et al., 2006); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10924277, 21811164, 10832578, 12855228, 16007612, 27287710, 27535533) (less)
|
|
|
Pathogenic
(Feb 10, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
ALG6-congenital disorder of glycosylation 1C
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004197233.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Likely pathogenic
(Oct 19, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
ALG6-congenital disorder of glycosylation 1C
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002775775.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
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Pathogenic
(Nov 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
ALG6-congenital disorder of glycosylation 1C
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002242053.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant, c.897_899del, results in the deletion of 1 amino acid(s) of the ALG6 protein (p.Ile299del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.897_899del, results in the deletion of 1 amino acid(s) of the ALG6 protein (p.Ile299del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753111873, gnomAD 0.006%). This variant has been observed in individual(s) with congenital disorder of glycosylation 1c (PMID: 10924277, 27287710). 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: 30420). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Jul 01, 2000)
|
no assertion criteria provided
Method: literature only
|
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ic
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000026017.3
First in ClinVar: Apr 04, 2013 Last updated: Apr 21, 2017 |
Comment on evidence:
In a patient with CDG Ic (CDG1C; 603147), Westphal et al. (2000) identified compound heterozygosity for 2 pathogenic mutations in the ALG6 gene: a splice … (more)
In a patient with CDG Ic (CDG1C; 603147), Westphal et al. (2000) identified compound heterozygosity for 2 pathogenic mutations in the ALG6 gene: a splice site mutation resulting in the skipping of exon 3 (604566.0003) inherited from the mother, and a 3-bp deletion (895delATA) resulting in deletion of ile299 within a transmembrane domain inherited from the father. The allele with the 3-bp deletion also carried an F304S polymorphism. Functional expression studies showed that although the paternal allele with the 3-bp deletion and F304S was able to almost completely rescue the glycosylation defect in yeast, it produced an inefficiently transcribed or unstable mRNA with reduced expression. (less)
|
|
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809140.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
|
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742002.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974002.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
Comment:
Comment:
This variant, c.897_899del, results in the deletion of 1 amino acid(s) of the ALG6 protein (p.Ile299del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753111873, gnomAD 0.006%). This variant has been observed in individual(s) with congenital disorder of glycosylation 1c (PMID: 10924277, 27287710). 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: 30420). For these reasons, this variant has been classified as Pathogenic.
Germline Functional Evidence
| 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. |
Comment:
In-frame deletion of one amino acid in a non-repeat region; Commonly identified and reported variant in patients with CDG-Ic (Hanefeld et al., 2000; Sun et al., 2005; Morava et al., 2006); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10924277, 21811164, 10832578, 12855228, 16007612, 27287710, 27535533)
Comment:
This variant, c.897_899del, results in the deletion of 1 amino acid(s) of the ALG6 protein (p.Ile299del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753111873, gnomAD 0.006%). This variant has been observed in individual(s) with congenital disorder of glycosylation 1c (PMID: 10924277, 27287710). 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: 30420). For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. | Morava E | Journal of inherited metabolic disease | 2016 | PMID: 27287710 |
| Analysis of multiple mutations in the hALG6 gene in a patient with congenital disorder of glycosylation Ic. | Westphal V | Molecular genetics and metabolism | 2000 | PMID: 10924277 |
Text-mined citations for rs387906338 ...
HelpThese 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 Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.