NM_001458.5(FLNC):c.7906A>T (p.Ser2636Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 22, 2022
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:: RCV000688514.7

Allele description [Variation Report for NM_001458.5(FLNC):c.7906A>T (p.Ser2636Cys)]

NM_001458.5(FLNC):c.7906A>T (p.Ser2636Cys)

Genes:

FLNC-AS1:FLNC antisense RNA 1 [Gene - HGNC]
FLNC:filamin C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_001458.5(FLNC):c.7906A>T (p.Ser2636Cys)

HGVS:

NC_000007.14:g.128858133A>T
NG_011807.1:g.32705A>T
NM_001127487.2:c.7807A>T
NM_001458.5:c.7906A>TMANE SELECT
NP_001120959.1:p.Ser2603Cys
NP_001449.3:p.Ser2636Cys
NP_001449.3:p.Ser2636Cys
LRG_870t1:c.7906A>T
LRG_870:g.32705A>T
LRG_870p1:p.Ser2636Cys
NC_000007.13:g.128498187A>T
NM_001458.4:c.7906A>T

Protein change:

S2603C

Links:

dbSNP: rs1563005954

NCBI 1000 Genomes Browser:

rs1563005954

Molecular consequence:

NM_001127487.2:c.7807A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001458.5:c.7906A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Myofibrillar myopathy 5
Synonyms:: FILAMINOPATHY, AUTOSOMAL DOMINANT; Myofibrillar myopathy, filamin C-related; Filaminopathy (type)
Identifiers:: MONDO: MONDO:0012289; MedGen: C1836050; OMIM: 609524

Name:: Distal myopathy with posterior leg and anterior hand involvement
Synonyms:: WILLIAMS DISTAL MYOPATHY; Myopathy, distal, 4
Identifiers:: MONDO: MONDO:0013550; MedGen: C3279722; Orphanet: 63273; OMIM: 614065

Name:: Hypertrophic cardiomyopathy 26
Synonyms:: Cardiomyopathy, familial hypertrophic, 26
Identifiers:: MONDO: MONDO:0014883; MedGen: C4310749; Orphanet: 75249; OMIM: 617047

Name:: Dilated Cardiomyopathy, Dominant
Identifiers:: MedGen: CN239310

Recent activity

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putative glucose-6-phosphate 1-epimerase [Mangifera indica]
putative glucose-6-phosphate 1-epimerase [Mangifera indica]
gi|2118907766|ref|XP_044484388.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000816130	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000816130

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 22, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000816130.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 568227). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2636 of the FLNC protein (p.Ser2636Cys).

#	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

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