NM_001079802.2(FKTN):c.530A>G (p.His177Arg) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV001954774.4

Allele description [Variation Report for NM_001079802.2(FKTN):c.530A>G (p.His177Arg)]

NM_001079802.2(FKTN):c.530A>G (p.His177Arg)

Gene:

FKTN:fukutin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q31.2

Genomic location:

Preferred name:

NM_001079802.2(FKTN):c.530A>G (p.His177Arg)

HGVS:

NC_000009.12:g.105604375A>G
NG_008754.1:g.51246A>G
NM_001079802.2:c.530A>GMANE SELECT
NM_001198963.2:c.530A>G
NM_001351496.2:c.530A>G
NM_001351497.2:c.461A>G
NM_001351498.2:c.530A>G
NM_001351499.2:c.134A>G
NM_001351500.2:c.134A>G
NM_001351501.2:c.134A>G
NM_001351502.2:c.134A>G
NM_006731.2:c.530A>G
NP_001073270.1:p.His177Arg
NP_001185892.1:p.His177Arg
NP_001338425.1:p.His177Arg
NP_001338426.1:p.His154Arg
NP_001338427.1:p.His177Arg
NP_001338428.1:p.His45Arg
NP_001338429.1:p.His45Arg
NP_001338430.1:p.His45Arg
NP_001338431.1:p.His45Arg
NP_006722.2:p.His177Arg
LRG_434t2:c.530A>G
LRG_434:g.51246A>G
LRG_434p2:p.His177Arg
NC_000009.11:g.108366656A>G
NR_147213.2:n.745A>G
NR_147214.2:n.653A>G

Protein change:

H154R

Links:

dbSNP: rs773322779

NCBI 1000 Genomes Browser:

rs773322779

Molecular consequence:

NM_001079802.2:c.530A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001198963.2:c.530A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351496.2:c.530A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351497.2:c.461A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351498.2:c.530A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351499.2:c.134A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351500.2:c.134A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351501.2:c.134A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351502.2:c.134A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006731.2:c.530A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_147213.2:n.745A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147214.2:n.653A>G - 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
SCV002201028	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2021)	germline	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

SCV002201028

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2021)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002201028.2

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

Description

This sequence change replaces histidine with arginine at codon 177 of the FKTN protein (p.His177Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Mar 30, 2024

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