VCV000488521.5 - ClinVar

NM_181789.4(GLDN):c.1305G>A (p.Trp435Ter)

Germline

Classification

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.

(4)

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

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_181789.4(GLDN):c.1305G>A (p.Trp435Ter)

Variation ID: 488521 Accession: VCV000488521.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q21.2 15: 51404403 (GRCh38) [ NCBI UCSC ] 15: 51696600 (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	Feb 8, 2018	May 12, 2018	Jan 12, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_181789.4:c.1305G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_861454.2:p.Trp435Ter	nonsense
NM_001330297.2:c.933G>A	NP_001317226.1:p.Trp311Ter	nonsense
NC_000015.10:g.51404403G>A
NC_000015.9:g.51696600G>A
NG_054933.1:g.67888G>A

... more HGVS ... less HGVS

Protein change

W435*, W311*

Other names

Canonical SPDI

NC_000015.10:51404402:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

The Genome Aggregation Database (gnomAD), exomes 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Exome Aggregation Consortium (ExAC) 0.00003

The Genome Aggregation Database (gnomAD) 0.00001

Links

ClinGen: CA7560725 dbSNP: rs775011495 VarSome

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
Gene	OMIM	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.
GLDN		-	-	GRCh38 GRCh37	119	150

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.
Lethal congenital contracture syndrome 11	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 12, 2018	RCV000578440.7
Flexion contracture	Likely pathogenic (1)	criteria provided, single submitter	Jan 1, 2017	RCV000627012.2
Breathing dysregulation Congenital contracture Polyhydramnios	Likely pathogenic (1)	criteria provided, single submitter	Jan 1, 2017	RCV000627011.2

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.
Pathogenic (Dec 09, 2017)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Lethal congenital contracture syndrome 11 (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV000680245.1 First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018	Publications: PubMed (1) PubMed: 28726266 Sex: male Tissue: blood
Likely pathogenic (Jan 01, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breathing dysregulation Congenital contracture Polyhydramnios Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000747714.1 First in ClinVar: May 12, 2018 Last updated: May 12, 2018
Likely pathogenic (Jan 01, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Flexion contracture Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000747715.1 First in ClinVar: May 12, 2018 Last updated: May 12, 2018
Pathogenic (Jan 12, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lethal congenital contracture syndrome 11 Affected status: yes Allele origin: inherited	Center of Genomic medicine, Geneva, University Hospital of Geneva Accession: SCV000840416.1 First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018	Comment: This variant was identified in a homozygous state in two newborn babies deceased shortly after birth. Both parents are heterozygous carriers of this variant. Number of individuals with the variant: 2 Age: 0-9 years Sex: female

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Survival among children with "Lethal" congenital contracture syndrome 11 caused by novel mutations in the gliomedin gene (GLDN).	Wambach JA	Human mutation	2017	PMID: 28726266

Text-mined citations for rs775011495 ...

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 Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_181789.4(GLDN):c.1305G>A (p.Trp435Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs775011495 ...