NM_025099.6(CTC1):c.724_727del (p.Lys242fs) AND Dyskeratosis congenita

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV000456770.11

Allele description [Variation Report for NM_025099.6(CTC1):c.724_727del (p.Lys242fs)]

NM_025099.6(CTC1):c.724_727del (p.Lys242fs)

Gene:

CTC1:CST telomere replication complex component 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_025099.6(CTC1):c.724_727del (p.Lys242fs)

Other names:

p.Lys242Leufs*41

HGVS:

NC_000017.11:g.8237442_8237445del
NG_032148.2:g.15653_15656del
NM_025099.6:c.724_727delMANE SELECT
NP_079375.3:p.Lys242fs
LRG_1124t1:c.724_727del
LRG_1124:g.15653_15656del
LRG_1124p1:p.Lys242fs
NC_000017.10:g.8140758_8140761del
NC_000017.10:g.8140760_8140763del
NM_025099.5:c.724_727delAAAG
NM_025099.6:c.724_727delAAAGMANE SELECT

Protein change:

K242fs

Links:

OMIM: 613129.0001; dbSNP: rs199473674

NCBI 1000 Genomes Browser:

rs199473674

Molecular consequence:

NM_025099.6:c.724_727del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000541114	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22267198, 22387016, 22532422, 22899577, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541114

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (5)
[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

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.

Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS, Urquhart JE, Daly SB, Dickerson JE, O'Sullivan J, Leibundgut EO, Muter J, Abdel-Salem GM, Babul-Hirji R, Baxter P, Berger A, Bonafé L, Brunstom-Hernandez JE, Buckard JA, Chitayat D, Chong WK, Cordelli DM, et al.

Nat Genet. 2012 Jan 22;44(3):338-42. doi: 10.1038/ng.1084.

PubMed [citation]

PMID:: 22267198

Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts.

Polvi A, Linnankivi T, Kivelä T, Herva R, Keating JP, Mäkitie O, Pareyson D, Vainionpää L, Lahtinen J, Hovatta I, Pihko H, Lehesjoki AE.

Am J Hum Genet. 2012 Mar 9;90(3):540-9. doi: 10.1016/j.ajhg.2012.02.002. Epub 2012 Mar 1.

PubMed [citation]

PMID:: 22387016
PMCID:: PMC3309194

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000541114.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Lys242Leufs*41) in the CTC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTC1 are known to be pathogenic (PMID: 22267198, 22387016). This variant is present in population databases (rs199473674, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with CTC1-related conditions (PMID: 22267198, 22387016, 22532422, 22899577). ClinVar contains an entry for this variant (Variation ID: 30995). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: May 1, 2024

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