NM_001457.4(FLNB):c.4781A>C (p.Tyr1594Ser) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 20, 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:: RCV003555090.2

Allele description [Variation Report for NM_001457.4(FLNB):c.4781A>C (p.Tyr1594Ser)]

NM_001457.4(FLNB):c.4781A>C (p.Tyr1594Ser)

Gene:

FLNB:filamin B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p14.3

Genomic location:

Preferred name:

NM_001457.4(FLNB):c.4781A>C (p.Tyr1594Ser)

HGVS:

NC_000003.12:g.58136088A>C
NG_012801.1:g.132689A>C
NM_001164317.2:c.4874A>C
NM_001164318.2:c.4781A>C
NM_001164319.2:c.4781A>C
NM_001457.4:c.4781A>CMANE SELECT
NP_001157789.1:p.Tyr1625Ser
NP_001157790.1:p.Tyr1594Ser
NP_001157791.1:p.Tyr1594Ser
NP_001448.2:p.Tyr1594Ser
NP_001448.2:p.Tyr1594Ser
NC_000003.11:g.58121815A>C
NM_001457.2:c.4781A>C

Protein change:

Y1594S

Molecular consequence:

NM_001164317.2:c.4874A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001164318.2:c.4781A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001164319.2:c.4781A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001457.4:c.4781A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293112	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 20, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22190451, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293112

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 20, 2023)

germline

clinical testing

PubMed (2)
[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

Disease-associated mutations in the actin-binding domain of filamin B cause cytoplasmic focal accumulations correlating with disease severity.

Daniel PB, Morgan T, Alanay Y, Bijlsma E, Cho TJ, Cole T, Collins F, David A, Devriendt K, Faivre L, Ikegawa S, Jacquemont S, Jesic M, Krakow D, Liebrecht D, Maitz S, Marlin S, Morin G, Nishikubo T, Nishimura G, Prescott T, Scarano G, et al.

Hum Mutat. 2012 Apr;33(4):665-73. doi: 10.1002/humu.22012. Epub 2012 Jan 23.

PubMed [citation]

PMID:: 22190451

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, SCV004293112.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLNB protein function. This missense change has been observed in individual(s) with Larsen syndrome (PMID: 22190451; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 1594 of the FLNB protein (p.Tyr1594Ser).

#	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

ClinVar

Relating variation to medicine