VCV002443747.1 - ClinVar

NM_001753.5(CAV1):c.237_238del (p.His79fs)

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.

(1)

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001753.5(CAV1):c.237_238del (p.His79fs)

Variation ID: 2443747 Accession: VCV002443747.1

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 7q31.2 7: 116558982-116558983 (GRCh38) [ NCBI UCSC ] 7: 116199036-116199037 (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	Mar 18, 2023	Mar 18, 2023	Feb 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001753.5:c.237_238del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001744.2:p.His79fs	frameshift
NM_001172895.1:c.144_145del	NP_001166366.1:p.His48fs	frameshift
NM_001172896.2:c.144_145del	NP_001166367.1:p.His48fs	frameshift
NM_001172897.2:c.144_145del	NP_001166368.1:p.His48fs	frameshift
NC_000007.14:g.116558983CA[2]
NC_000007.13:g.116199037CA[2]
NG_012051.1:g.39199CA[2]

... more HGVS ... less HGVS

Protein change

H48fs, H79fs

Other names

Canonical SPDI

NC_000007.14:116558981:ACACACA:ACACA

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.

Links

OMIM: 601047.0007 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.
CAV1		-	-	GRCh38 GRCh37	109	162

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.
Congenital generalized lipodystrophy type 3	Pathogenic (1)	no assertion criteria provided	Feb 14, 2023	RCV003152354.1

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 (Feb 14, 2023)	no assertion criteria provided Method: literature only	LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV003840944.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (1) PubMed: 34643546 Comment on evidence: In 4 members of a large consanguineous family of Turkish descent with congenital generalized lipodystrophy type 3 (CGL3; 612526), Karhan et al. (2021) identified a … (more) In 4 members of a large consanguineous family of Turkish descent with congenital generalized lipodystrophy type 3 (CGL3; 612526), Karhan et al. (2021) identified a homozygous 2-bp deletion (c.237_238del) in exon 3 of the CAV1 gene, resulting in a frameshift and premature termination (His79GlnfsTer3). The mutation, which was identified by sequencing of a panel of genes involved in lipodystrophy or insulin resistance syndromes, was present in the 7 unaffected parents who were tested. The variant was not present in the ExAC and gnomAD databases. By studying cultured skin fibroblasts from one patient, Karhan et al. (2021) found complete loss of protein expression of caveolin-1 and its partners caveolin-2 and cavin-1 and absence of caveolae at the plasma membrane. The fibroblasts also showed insulin resistance, increased oxidative stress, and premature senescence. (less)

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
Biallelic CAV1 null variants induce congenital generalized lipodystrophy with achalasia.	Karhan AN	European journal of endocrinology	2021	PMID: 34643546

Text-mined citations for this variant ...

Record last updated Apr 23, 2023

ClinVar Genomic variation as it relates to human health

NM_001753.5(CAV1):c.237_238del (p.His79fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...