NM_001458.5(FLNC):c.1994_1995delinsAA (p.Cys665Ter) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 24, 2023
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:: RCV003301922.2

Allele description [Variation Report for NM_001458.5(FLNC):c.1994_1995delinsAA (p.Cys665Ter)]

NM_001458.5(FLNC):c.1994_1995delinsAA (p.Cys665Ter)

Gene:

FLNC:filamin C [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_001458.5(FLNC):c.1994_1995delinsAA (p.Cys665Ter)

HGVS:

NC_000007.14:g.128841350_128841351delinsAA
NG_011807.1:g.15922_15923delinsAA
NM_001127487.2:c.1994_1995delinsAA
NM_001458.5:c.1994_1995delinsAAMANE SELECT
NP_001120959.1:p.Cys665Ter
NP_001449.3:p.Cys665Ter
NP_001449.3:p.Cys665Ter
LRG_870t1:c.1994_1995delGCinsAA
LRG_870:g.15922_15923delinsAA
LRG_870p1:p.Cys665Ter
NC_000007.13:g.128481404_128481405delinsAA
NM_001458.4:c.1994_1995delGCinsAA

Protein change:

C665*

Molecular consequence:

NM_001127487.2:c.1994_1995delinsAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001458.5:c.1994_1995delinsAA - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004004605	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 24, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004004605

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 24, 2023)

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

Details of each submission

From Ambry Genetics, SCV004004605.2

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

Description

The c.1994_1995delGCinsAA pathogenic mutation (also known as p.C665*), located in coding exon 12 of the FLNC gene, results from a deletion of GC and insertion of AA at nucleotide positions 1994 to 1995. This changes the amino acid from a cysteine to a stop codon within coding exon 12. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is expected to be causative of FLNC-related dilated cardiomyopathy; however, its clinical significance for FLNC-related hypertrophy/restrictive cardiomyopathy and/or skeletal myopathy is unclear.

#	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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