NM_025099.6(CTC1):c.2164C>T (p.Pro722Ser) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001819346.5

Allele description [Variation Report for NM_025099.6(CTC1):c.2164C>T (p.Pro722Ser)]

NM_025099.6(CTC1):c.2164C>T (p.Pro722Ser)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_025099.6(CTC1):c.2164C>T (p.Pro722Ser)

HGVS:

NC_000017.11:g.8232124G>A
NG_032148.2:g.20972C>T
NM_025099.6:c.2164C>TMANE SELECT
NP_079375.3:p.Pro722Ser
LRG_1124t1:c.2164C>T
LRG_1124:g.20972C>T
LRG_1124p1:p.Pro722Ser
NC_000017.10:g.8135442G>A
NM_025099.5:c.2164C>T
NR_046431.2:n.2079C>T

Protein change:

P722S

Links:

dbSNP: rs770505786

NCBI 1000 Genomes Browser:

rs770505786

Molecular consequence:

NM_025099.6:c.2164C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046431.2:n.2079C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002065665	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 13, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004242074	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002065665

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 13, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004242074

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes.

Arias-Salgado EG, Galvez E, Planas-Cerezales L, Pintado-Berninches L, Vallespin E, Martinez P, Carrillo J, Iarriccio L, Ruiz-Llobet A, Catalá A, Badell-Serra I, Gonzalez-Granado LI, Martín-Nalda A, Martínez-Gallo M, Galera-Miñarro A, Rodríguez-Vigil C, Bastos-Oreiro M, Perez de Nanclares G, Leiro-Fernández V, Uria ML, Diaz-Heredia C, Valenzuela C, et al.

Orphanet J Rare Dis. 2019 Apr 17;14(1):82. doi: 10.1186/s13023-019-1046-0.

PubMed [citation]

PMID:: 30995915
PMCID:: PMC6471801

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002065665.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004242074.1

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

Description

Variant summary: CTC1 c.2164C>T (p.Pro722Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-05 in 168732 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2164C>T has been reported in the literature in at-least one individuals affected with pulmonary fibrosis (example: Arias-Salgado_2019). This report does not provide unequivocal conclusions about association of the variant with Cerebroretinal Microangiopathy With Calcifications And Cysts 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 30995915). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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 7, 2024

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