NM_001079802.2(FKTN):c.1167dup (p.Phe390fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 31, 2024
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:: RCV000634081.17

Allele description [Variation Report for NM_001079802.2(FKTN):c.1167dup (p.Phe390fs)]

NM_001079802.2(FKTN):c.1167dup (p.Phe390fs)

Gene:

FKTN:fukutin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

9q31.2

Genomic location:

Preferred name:

NM_001079802.2(FKTN):c.1167dup (p.Phe390fs)

HGVS:

NC_000009.11:g.108382330_108382331insA
NC_000009.12:g.105620056dup
NG_008754.1:g.66927dup
NM_001079802.2:c.1167dupMANE SELECT
NM_001198963.2:c.1167dup
NM_001351496.2:c.1167dup
NM_001351497.2:c.1098dup
NM_001351498.2:c.1167dup
NM_001351499.2:c.771dup
NM_001351500.2:c.771dup
NM_001351501.2:c.771dup
NM_001351502.2:c.771dup
NM_006731.2:c.1167dup
NP_001073270.1:p.Phe390fs
NP_001185892.1:p.Phe390fs
NP_001338425.1:p.Phe390fs
NP_001338426.1:p.Phe367fs
NP_001338427.1:p.Phe390fs
NP_001338428.1:p.Phe258fs
NP_001338429.1:p.Phe258fs
NP_001338430.1:p.Phe258fs
NP_001338431.1:p.Phe258fs
NP_006722.2:p.Phe390fs
LRG_434t2:c.1167dup
LRG_434:g.66927dup
LRG_434p2:p.Phe390fs
NC_000009.11:g.108382330_108382331insA
NC_000009.11:g.108382337dup
NC_000009.11:g.108382337dupA
NM_001079802.1:c.1167dupA
NM_001079802.2:c.1167dup
NM_006731.2:c.1167dupA
NR_147213.2:n.1118dup
NR_147214.2:n.1290dup
c.1167dupA (p.Phe390Ilefs*14)
c.1167insA

Note:

NCBI staff reviewed the sequence information reported in PubMed 10545611 Fig. 3 to determine the location of this allele on the current reference sequence.

Protein change:

F258fs

Links:

Genetic Testing Registry (GTR): GTR000531545; Genetic Testing Registry (GTR): GTR000570054; OMIM: 607440.0005; dbSNP: rs398123555

NCBI 1000 Genomes Browser:

rs398123555

Molecular consequence:

NM_001079802.2:c.1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001198963.2:c.1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351496.2:c.1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351497.2:c.1098dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351498.2:c.1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351499.2:c.771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351500.2:c.771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351501.2:c.771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351502.2:c.771dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006731.2:c.1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_147213.2:n.1118dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147214.2:n.1290dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Walker-Warburg congenital muscular dystrophy
Synonyms:: Muscular dystrophy-dystroglycanopathy, type A; Walker-Warburg syndrome
Identifiers:: MONDO: MONDO:0000171; MedGen: C0265221; Orphanet: 899; OMIM: PS236670

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000755359	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17878207, 18177472, 18752264, 19266496, 27065010, 28492532
SCV002081970	Natera, Inc.	no assertion criteria provided	Pathogenic (Apr 3, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000755359

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002081970

Natera, Inc.

no assertion criteria provided

Pathogenic
(Apr 3, 2020)

germline

clinical testing

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

Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan.

Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B, Straub V, Robb S, Quinlivan R, Feng L, Jimenez-Mallebrera C, Mercuri E, Manzur AY, Kinali M, Torelli S, Brown SC, Sewry CA, Bushby K, Topaloglu H, North K, Abbs S, Muntoni F.

Brain. 2007 Oct;130(Pt 10):2725-35. Epub 2007 Sep 18.

PubMed [citation]

PMID:: 17878207

Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.

Cotarelo RP, Valero MC, Prados B, Peña A, Rodríguez L, Fano O, Marco JJ, Martínez-Frías ML, Cruces J.

Clin Genet. 2008 Feb;73(2):139-45. doi: 10.1111/j.1399-0004.2007.00936.x. Epub 2007 Dec 19.

PubMed [citation]

PMID:: 18177472

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000755359.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Phe390Ilefs*14) in the FKTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 72 amino acid(s) of the FKTN protein. This variant is present in population databases (rs756763804, gnomAD 0.8%). This premature translational stop signal has been observed in individual(s) with dystroglycanopathies (PMID: 17878207, 18177472, 18752264, 19266496, 27065010). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3203). 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

From Natera, Inc., SCV002081970.1

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

#	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: Jul 7, 2024

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