NM_001330.5(CTF1):c.591C>G (p.Pro197=) AND not specified

Germline classification:: Benign (2 submissions)
Last evaluated:: Oct 15, 2018
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:: RCV000037158.7

Allele description [Variation Report for NM_001330.5(CTF1):c.591C>G (p.Pro197=)]

NM_001330.5(CTF1):c.591C>G (p.Pro197=)

Genes:

LOC130058878:ATAC-STARR-seq lymphoblastoid silent region 7400 [Gene]
CTF1:cardiotrophin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_001330.5(CTF1):c.591C>G (p.Pro197=)

HGVS:

NC_000016.10:g.30902524C>G
NG_009171.1:g.10918C>G
NM_001142544.3:c.588C>G
NM_001330.5:c.591C>GMANE SELECT
NP_001136016.1:p.Pro196=
NP_001321.1:p.Pro197=
NP_001321.1:p.Pro197=
LRG_408t1:c.591C>G
LRG_408:g.10918C>G
LRG_408p1:p.Pro197=
NC_000016.9:g.30913845C>G
NM_001330.3:c.591C>G
NR_165660.1:n.729C>G
c.591C>G
p.Pro197Pro

Links:

dbSNP: rs397516652

NCBI 1000 Genomes Browser:

rs397516652

Molecular consequence:

NR_165660.1:n.729C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001142544.3:c.588C>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001330.5:c.591C>G - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

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
SCV000060815	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Dec 22, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000919252	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Oct 15, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060815

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Benign
(Dec 22, 2014)

germline

clinical testing

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

SCV000919252

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Oct 15, 2018)

germline

clinical testing

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	not provided	8	8	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060815.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	8	not provided	not provided	clinical testing	PubMed (1)

Description

p.Pro197Pro in exon 3 of CTF1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.9% (28/3168) of Eur opean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs397516652)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		8	not provided	8	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919252.1

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

Description

Variant summary: CTF1 c.591C>G results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 131558 control chromosomes (gnomAD). The observed variant frequency is approximately 72-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in CTF1 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.591C>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant once as uncertain significance and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.

#	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: Feb 25, 2025

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