NM_001099274.3(TINF2):c.860T>C (p.Leu287Pro) AND Dyskeratosis congenita

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 26, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001852639.5

Allele description [Variation Report for NM_001099274.3(TINF2):c.860T>C (p.Leu287Pro)]

NM_001099274.3(TINF2):c.860T>C (p.Leu287Pro)

Gene:

TINF2:TERF1 interacting nuclear factor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_001099274.3(TINF2):c.860T>C (p.Leu287Pro)

HGVS:

NC_000014.9:g.24240620A>G
NG_016650.1:g.7055T>C
NG_054634.1:g.13204A>G
NM_001099274.3:c.860T>CMANE SELECT
NM_001363668.2:c.755T>C
NM_012461.3:c.860T>C
NP_001092744.1:p.Leu287Pro
NP_001350597.1:p.Leu252Pro
NP_036593.2:p.Leu287Pro
LRG_342t1:c.860T>C
LRG_342t2:c.860T>C
LRG_342:g.7055T>C
LRG_342p1:p.Leu287Pro
LRG_342p2:p.Leu287Pro
NC_000014.8:g.24709826A>G
NM_001099274.1:c.860T>C

Protein change:

L252P

Links:

dbSNP: rs199422316

NCBI 1000 Genomes Browser:

rs199422316

Molecular consequence:

NM_001099274.3:c.860T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363668.2:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_012461.3:c.860T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dyskeratosis congenita
Identifiers:: MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550

Recent activity

Clear Turn Off Turn On

MMP17 [Nomascus leucogenys]
MMP17 [Nomascus leucogenys]
Gene ID:100588007

Gene
LOC8072292 [Sorghum bicolor]
LOC8072292 [Sorghum bicolor]
Gene ID:8072292

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002275068	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 26, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22211879, 18669893, 26083318, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002275068

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 26, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterization of interactions between naturally mutated forms of the TIN2 protein and its known protein partners of the shelterin complex.

Xin ZT, Ly H.

Clin Genet. 2012 Mar;81(3):301-2. doi: 10.1111/j.1399-0004.2011.01784.x. Epub 2011 Dec 30. No abstract available.

PubMed [citation]

PMID:: 22211879

TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes.

Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I.

Blood. 2008 Nov 1;112(9):3594-600. doi: 10.1182/blood-2008-05-153445. Epub 2008 Jul 30.

PubMed [citation]

PMID:: 18669893
PMCID:: PMC2572788

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002275068.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 287 of the TINF2 protein (p.Leu287Pro). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TINF2 function (PMID: 22211879). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 38924). This missense change has been observed in individual(s) with clinical features of dyskeratosis congenita (PMID: 18669893, 26083318; Invitae). In at least one individual the variant was observed to be de novo.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine