Submissions for variant NM_024301.5(FKRP):c.822C>G (p.Ile274Met)

gnomAD frequency: 0.00251  dbSNP: rs77138370

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086481	SCV000290703	likely benign	Walker-Warburg congenital muscular dystrophy	2025-02-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000117039	SCV000314272	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000117039	SCV000337230	benign	not specified	2015-12-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000711666	SCV000519103	likely benign	not provided	2021-05-20	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27142102)
Athena Diagnostics	RCV000117039	SCV000842053	likely benign	not specified	2023-10-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000711666	SCV000885460	likely benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001836732	SCV002097986	uncertain significance	Muscular dystrophy-dystroglycanopathy type B5; Autosomal recessive limb-girdle muscular dystrophy type 2I; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5	2020-06-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426662	SCV002680934	benign	Cardiovascular phenotype	2019-03-26	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000117039	SCV005885364	likely benign	not specified	2025-02-24	criteria provided, single submitter	clinical testing	Variant summary: FKRP c.822C>G (p.Ile274Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00069 in 114982 control chromosomes, predominantly at a frequency of 0.0096 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in FKRP causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.0024). To our knowledge, no occurrence of c.822C>G in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 129058). Based on the evidence outlined above, the variant was classified as likely benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000117039	SCV006067075	likely benign	not specified	2025-04-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000117039	SCV000151165	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Clinical Genetics, Academic Medical Center	RCV000117039	SCV001919919	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000117039	SCV001967758	benign	not specified		no assertion criteria provided	clinical testing