VCV001691272.2 - ClinVar

NM_001102401.4(TTI2):c.950A>T (p.Asp317Val)

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001102401.4(TTI2):c.950A>T (p.Asp317Val)

Variation ID: 1691272 Accession: VCV001691272.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 8p12 8: 33503913 (GRCh38) [ NCBI UCSC ] 8: 33361431 (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	Dec 3, 2022	Jun 24, 2023	Jun 21, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001102401.4:c.950A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001095871.1:p.Asp317Val	missense
NM_001265581.2:c.950A>T	NP_001252510.1:p.Asp317Val	missense
NM_001330505.3:c.857A>T	NP_001317434.1:p.Asp286Val	missense
NM_025115.5:c.950A>T	NP_079391.2:p.Asp317Val	missense
NC_000008.11:g.33503913T>A
NC_000008.10:g.33361431T>A
NG_033257.1:g.14273A>T

... more HGVS ... less HGVS

Protein change

D286V, D317V

Other names

Canonical SPDI

NC_000008.11:33503912:T: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

OMIM: 614426.0004 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.
TTI2		-	-	GRCh38 GRCh37	84	165

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.
Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome	Pathogenic/Likely pathogenic (2)	no assertion criteria provided	Jun 21, 2023	RCV002463372.4

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 (Oct 29, 2021)	no assertion criteria provided Method: clinical testing	Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome Affected status: yes Allele origin: inherited	Service de Biologie Medicale, CIUSSS du Saguenay-Lac-Saint-Jean Accession: SCV002525508.1 First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 Comment: Observed in 3 individuals in the homozygous state from 3 independant families in the Saguenay-Lac-St-Jean region of Québec, Canada.	Number of individuals with the variant: 13 Clinical Features: microcephaly (present) , strabismus (present) , global developmental delay (present) , severe intellectual disability (present) , absent speech (present) , epilepsy (present) , small stature … (more) microcephaly (present) , strabismus (present) , global developmental delay (present) , severe intellectual disability (present) , absent speech (present) , epilepsy (present) , small stature (present) , low weight (present) , slender build (present) , pyloric stenosis (present) , pulmonary valve stenosis (present) , brain anomaly at MRI (present) , dysmorphic facial features (present) , receding forehead (present) , deep set eyes (present) , dysplastic ears (present) , synophris (present) , prominent nose tip (present) , everted inferior lip (present) , narrow and ovale palate (present) , prominent upper central incisor (present) , retracted lower arch (present) , fine hair (present) , lentigines on the face (present) (less) Family history: yes
Pathogenic (Jun 21, 2023)	no assertion criteria provided Method: literature only	INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 39 Affected status: not provided Allele origin: germline	OMIM Accession: SCV003935021.1 First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023	Publications: PubMed (1) PubMed: 31290144 Comment on evidence: For discussion of the c.950A-T transversion (c.950A-T, NM_001265581.1) in the TTI2 gene, resulting in an asp317-to-val (D317V) substitution, that was identified in compound heterozygous state … (more) For discussion of the c.950A-T transversion (c.950A-T, NM_001265581.1) in the TTI2 gene, resulting in an asp317-to-val (D317V) substitution, that was identified in compound heterozygous state in a patient with autosomal recessive intellectual developmental disorder-39 (MRT39; 615541) by Ziegler et al. (2019), see 614426.0003. (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
Confirmation that variants in TTI2 are responsible for autosomal recessive intellectual disability.	Ziegler A	Clinical genetics	2019	PMID: 31290144

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_001102401.4(TTI2):c.950A>T (p.Asp317Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...