NM_024301.5(FKRP):c.1177G>A (p.Val393Ile) AND not provided

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Oct 20, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001093246.36

Allele description [Variation Report for NM_024301.5(FKRP):c.1177G>A (p.Val393Ile)]

NM_024301.5(FKRP):c.1177G>A (p.Val393Ile)

Gene:

FKRP:fukutin related protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.1177G>A (p.Val393Ile)

Other names:

p.V393I:GTA>ATA

HGVS:

NC_000019.10:g.46756627G>A
NG_008898.2:g.15582G>A
NM_001039885.3:c.1177G>A
NM_024301.5:c.1177G>AMANE SELECT
NP_001034974.1:p.Val393Ile
NP_077277.1:p.Val393Ile
LRG_761t1:c.1177G>A
LRG_761:g.15582G>A
LRG_761p1:p.Val393Ile
NC_000019.9:g.47259884G>A
NM_024301.4:c.1177G>A

Protein change:

V393I

Links:

dbSNP: rs140679502

NCBI 1000 Genomes Browser:

rs140679502

Molecular consequence:

NM_001039885.3:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024301.5:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000613306	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Feb 17, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001250137	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Dec 1, 2019)	germline	clinical testing	Citation Link,
SCV002048979	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Oct 20, 2023)	germline	clinical testing	Citation Link,
SCV004225417	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Athena Diagnostics, SCV000613306.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001250137.26

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002048979.2

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

Description

The FKRP c.1177G>A; p.Val393Ile variant (rs140679502), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 137380). This variant is found in the African population with an allele frequency of 0.7% (162/24462 alleles, including 1 homozygote) in the Genome Aggregation Database. The valine at codon 393 is highly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.66). Due to limited information, the clinical significance of the p.Val393Ile variant is uncertain at this time. Gene specific statement: Pathogenic variants in FKRP are inherited in an autosomal recessive manner and are associated with muscular dystrophy-dystroglycanopathy types A5, B5 and C5 (MIM: 613153, 606612, and 607155). Symptomatic heterozygous carriers have also been reported at least once in the literature and present with a milder phenotype (Schottlaender et al. 2015).

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004225417.1

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

Description

BS1

#	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		1	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

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