NM_001110556.2(FLNA):c.145_146del (p.Phe49fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 10, 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:: RCV003804259.1

Allele description [Variation Report for NM_001110556.2(FLNA):c.145_146del (p.Phe49fs)]

NM_001110556.2(FLNA):c.145_146del (p.Phe49fs)

Gene:

FLNA:filamin A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110556.2(FLNA):c.145_146del (p.Phe49fs)

HGVS:

NC_000023.11:g.154371101_154371102del
NG_008677.1:g.1674_1675del
NG_011506.2:g.8538_8539del
NG_147834.1:g.187_188del
NM_001110556.2:c.145_146delMANE SELECT
NM_001456.4:c.145_146del
NP_001104026.1:p.Phe49fs
NP_001447.2:p.Phe49fs
LRG_1340t1:c.145_146del
LRG_1340:g.8538_8539del
LRG_1340p1:p.Phe49fs
LRG_745:g.1674_1675del
NC_000023.10:g.153599468_153599469del
NC_000023.10:g.153599469_153599470del

Protein change:

F49fs

Molecular consequence:

NM_001110556.2:c.145_146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001456.4:c.145_146del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004596007	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 10, 2023)	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

SCV004596007

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 10, 2023)

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, SCV004596007.1

#	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.Phe49Hisfs*56) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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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