NM_001110556.2(FLNA):c.2761C>T (p.Arg921Ter) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 9, 2021
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:: RCV001380531.5

Allele description

NM_001110556.2(FLNA):c.2761C>T (p.Arg921Ter)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.2761C>T (p.Arg921Ter)

HGVS:

NC_000023.11:g.154362044G>A
NG_011506.2:g.17595C>T
NM_001110556.2:c.2761C>TMANE SELECT
NM_001456.4:c.2761C>T
NP_001104026.1:p.Arg921Ter
NP_001447.2:p.Arg921Ter
NP_001447.2:p.Arg921Ter
LRG_1340t1:c.2761C>T
LRG_1340:g.17595C>T
LRG_1340p1:p.Arg921Ter
NC_000023.10:g.153590412G>A
NM_001110556.1:c.2761C>T
NM_001456.3:c.2761C>T
NP_001447.2:p.Arg921*

Protein change:

R921*

Links:

dbSNP: rs398123614

NCBI 1000 Genomes Browser:

rs398123614

Molecular consequence:

NM_001110556.2:c.2761C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001456.4:c.2761C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Heterotopia, periventricular, X-linked dominant (PVNH1)
Synonyms:: PERIVENTRICULAR NODULAR HETEROTOPIA 1; X-linked periventricular heterotopia; Heterotopia familial nodular; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010233; MedGen: C1848213; Orphanet: 2149; Orphanet: 82004; OMIM: 300049

Name:: Melnick-Needles syndrome (MNS)
Synonyms:: Melnick-Needles osteodysplasty; Osteodysplasty of Melnick and Needles
Identifiers:: MONDO: MONDO:0010650; MedGen: C0025237; Orphanet: 2484; OMIM: 309350

Name:: Oto-palato-digital syndrome, type II (OPD2)
Synonyms:: OPD II SYNDROME; Oto-palato-digital syndrome type 2; Andre syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010571; MedGen: C1844696; Orphanet: 669; Orphanet: 90652; OMIM: 304120

Name:: Frontometaphyseal dysplasia (FMD1)
Identifiers:: MONDO: MONDO:0015942; MedGen: C0265293; OMIM: PS305620

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001578614	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 9, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16684786, 20730588, 26471271, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001578614

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 9, 2021)

germline

clinical testing

PubMed (4)
[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

Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations.

Parrini E, Ramazzotti A, Dobyns WB, Mei D, Moro F, Veggiotti P, Marini C, Brilstra EH, Dalla Bernardina B, Goodwin L, Bodell A, Jones MC, Nangeroni M, Palmeri S, Said E, Sander JW, Striano P, Takahashi Y, Van Maldergem L, Leonardi G, Wright M, Walsh CA, et al.

Brain. 2006 Jul;129(Pt 7):1892-906. Epub 2006 May 9.

PubMed [citation]

PMID:: 16684786

Combined cardiological and neurological abnormalities due to filamin A gene mutation.

de Wit MC, de Coo IF, Lequin MH, Halley DJ, Roos-Hesselink JW, Mancini GM.

Clin Res Cardiol. 2011 Jan;100(1):45-50. doi: 10.1007/s00392-010-0206-y. Epub 2010 Aug 22.

PubMed [citation]

PMID:: 20730588
PMCID:: PMC3022162

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001578614.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg921*) in the FLNA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLNA are known to be pathogenic (PMID: 16684786, 20730588, 26471271). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 93752). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

#	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 26, 2024

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