NM_001173464.2(KIF21A):c.2861G>A (p.Arg954Gln) AND Congenital fibrosis of extraocular muscles type 1

Germline classification:: Pathogenic (2 submissions)
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:: RCV000002540.7

Allele description [Variation Report for NM_001173464.2(KIF21A):c.2861G>A (p.Arg954Gln)]

NM_001173464.2(KIF21A):c.2861G>A (p.Arg954Gln)

Gene:

KIF21A:kinesin family member 21A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q12

Genomic location:

Preferred name:

NM_001173464.2(KIF21A):c.2861G>A (p.Arg954Gln)

HGVS:

NC_000012.12:g.39332404C>T
NG_017067.1:g.115987G>A
NM_001173463.2:c.2822G>A
NM_001173464.2:c.2861G>AMANE SELECT
NM_001173465.2:c.2753G>A
NM_017641.4:c.2822G>A
NP_001166934.1:p.Arg941Gln
NP_001166935.1:p.Arg954Gln
NP_001166936.1:p.Arg918Gln
NP_060111.2:p.Arg941Gln
NC_000012.11:g.39726206C>T
NM_017641.3:c.2822G>A
Q7Z4S6:p.Arg954Gln

Protein change:

R918Q; ARG954GLN

Links:

UniProtKB: Q7Z4S6#VAR_019402; OMIM: 608283.0002; dbSNP: rs121912586

NCBI 1000 Genomes Browser:

rs121912586

Molecular consequence:

NM_001173463.2:c.2822G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001173464.2:c.2861G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001173465.2:c.2753G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_017641.4:c.2822G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital fibrosis of extraocular muscles type 1
Synonyms:: BLEPHAROPTOSIS WITH ABSENT EYE MOVEMENTS; OPHTHALMOPLEGIA, CONGENITAL; FEOM1 LOCUS
Identifiers:: MONDO: MONDO:0021083; MedGen: C1851102; OMIM: 135700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022698	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 14595441, 18332320
SCV002558987	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	inherited	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

SCV000022698

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2008)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV002558987

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

inherited

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Yamada K, Andrews C, Chan WM, McKeown CA, Magli A, de Berardinis T, Loewenstein A, Lazar M, O'Keefe M, Letson R, London A, Ruttum M, Matsumoto N, Saito N, Morris L, Del Monte M, Johnson RH, Uyama E, Houtman WA, de Vries B, Carlow TJ, Hart BL, et al.

Nat Genet. 2003 Dec;35(4):318-21. Epub 2003 Nov 2.

PubMed [citation]

PMID:: 14595441

Novel and recurrent KIF21A mutations in congenital fibrosis of the extraocular muscles type 1 and 3.

Lu S, Zhao C, Zhao K, Li N, Larsson C.

Arch Ophthalmol. 2008 Mar;126(3):388-94. doi: 10.1001/archopht.126.3.388.

PubMed [citation]

PMID:: 18332320

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000022698.3

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

Description

In patients with congenital fibrosis of extraocular muscles-1 (135700), Yamada et al. (2003) identified a G-to-A transition at nucleotide 2861 of the KIF21A gene, resulting in an arg954-to-gln (R954Q) substitution. The R954W (608283.0001) and R954Q mutations are located in the first and second nucleotide positions of codon 954, respectively.

Lu et al. (2008) identified a heterozygous R954Q mutation in affected members of a Chinese family with a phenotype consistent with CFEOM3 (CFEOM3B; see 135700) due to variable involvement and severity of ophthalmoplegia and ptosis. Five individuals had a classic phenotype with bilateral severe ptosis, restricted upgaze, and compensatory head position. By contrast, 3 individuals had at least 1 eye with mild ptosis, residual upgaze, or the ability to elevate above the midline. Two additional family members had varying ptosis without compensatory head position. Finally, 1 individual, who was an obligate carrier, had only subtle symptoms with mild limitation of vertical ocular motility without ptosis, strabismus, or compensatory head position.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV002558987.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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