VCV002186475.3 - ClinVar

NM_144596.4(TTC8):c.901_905del (p.Arg300_Ile301insTer)

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.

(2)

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_144596.4(TTC8):c.901_905del (p.Arg300_Ile301insTer)

Variation ID: 2186475 Accession: VCV002186475.3

Type and length

Deletion, 5 bp

Location

Cytogenetic: 14q31.3 14: 88861323-88861327 (GRCh38) [ NCBI UCSC ] 14: 89327667-89327671 (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, 2023	Jun 29, 2024	Apr 12, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_144596.4:c.901_905del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_653197.2:p.Arg300_Ile301insTer	nonsense
NM_001288781.1:c.949_953del	NP_001275710.1:p.Arg316_Ile317insTer	nonsense
NM_001288782.1:c.307_311del	NP_001275711.1:p.Arg102_Ile103insTer	nonsense
NM_001288783.1:c.184_188del	NP_001275712.1:p.Arg61_Ile62insTer	nonsense
NM_001366535.2:c.871_875del	NP_001353464.1:p.Arg290_Ile291insTer	nonsense
NM_001366536.2:c.781_785del	NP_001353465.1:p.Arg260_Ile261insTer	nonsense
NM_198309.3:c.871_875del	NP_938051.1:p.Arg290_Ile291insTer	nonsense
NM_198310.3:c.781_785del	NP_938052.1:p.Arg260_Ile261insTer	nonsense
NR_159362.2:n.988_992del		non-coding transcript variant
NC_000014.9:g.88861324_88861328del
NC_000014.8:g.89327668_89327672del
NG_008126.2:g.42172_42176del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000014.9:88861322:AATCTA: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.

Links

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.
TTC8		-	-	GRCh38 GRCh37	526	555

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.
Bardet-Biedl syndrome	Pathogenic (1)	criteria provided, single submitter	Apr 12, 2022	RCV002623277.3
Bardet-Biedl syndrome 8	Likely pathogenic (1)	criteria provided, single submitter	-	RCV004577961.1

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 (Apr 12, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Bardet-Biedl syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003505089.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024	Publications: PubMed (5) PubMed: 16308660‚ 16877420‚ 19797195‚ 21052717‚ 30886724 Comment: This sequence change creates a premature translational stop signal (p.Ile291) in the TTC8 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Ile291) in the TTC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC8 are known to be pathogenic (PMID: 16308660, 16877420, 19797195, 21052717, 30886724). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TTC8-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bardet-Biedl syndrome 8 Affected status: yes Allele origin: germline	DNA-diagnostics Laboratory, Research Centre For Medical Genetics Accession: SCV005061813.1 First in ClinVar: Jun 29, 2024 Last updated: Jun 29, 2024

Comment:

This sequence change creates a premature translational stop signal (p.Ile291*) in the TTC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC8 are known to be pathogenic (PMID: 16308660, 16877420, 19797195, 21052717, 30886724). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TTC8-related conditions. 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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A novel compound heterozygous mutation in TTC8 identified in a Japanese patient.	Sato S	Human genome variation	2019	PMID: 30886724
Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals.	Janssen S	Human genetics	2011	PMID: 21052717
Identification of 11 novel mutations in eight BBS genes by high-resolution homozygosity mapping.	Harville HM	Journal of medical genetics	2010	PMID: 19797195
Screening of the eight BBS genes in Tunisian families: no evidence of triallelism.	Smaoui N	Investigative ophthalmology & visual science	2006	PMID: 16877420
BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.	Stoetzel C	Journal of human genetics	2006	PMID: 16308660

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_144596.4(TTC8):c.901_905del (p.Arg300_Ile301insTer)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...