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

gnomAD frequency: 0.00150  dbSNP: rs140679502

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000192864	SCV000168555	likely benign	not specified	2018-02-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000192864	SCV000247378	uncertain significance	not specified	2014-07-08	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000192864	SCV000335985	likely benign	not specified	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000456138	SCV000559439	likely benign	Walker-Warburg congenital muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV001093246	SCV000613306	uncertain significance	not provided	2020-02-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001093246	SCV001250137	uncertain significance	not provided	2019-12-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001093246	SCV002048979	uncertain significance	not provided	2023-10-20	criteria provided, single submitter	clinical testing	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).
Ambry Genetics	RCV002336274	SCV002639713	benign	Cardiovascular phenotype	2019-01-29	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Duke University Health System Sequencing Clinic, Duke University Health System	RCV001275320	SCV003919050	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2I	2023-04-20	criteria provided, single submitter	research
Mayo Clinic Laboratories, Mayo Clinic	RCV001093246	SCV004225417	uncertain significance	not provided	2023-04-18	criteria provided, single submitter	clinical testing	BS1
PreventionGenetics, part of Exact Sciences	RCV003925237	SCV004750943	likely benign	FKRP-related condition	2019-06-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV001275320	SCV001460345	benign	Autosomal recessive limb-girdle muscular dystrophy type 2I	2020-01-10	no assertion criteria provided	clinical testing