Submissions for variant NM_024301.5(FKRP):c.822C>G (p.Ile274Met) (rs77138370)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001086481	SCV000290703	likely benign	Walker-Warburg congenital muscular dystrophy	2019-12-31	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000117039	SCV000314272	benign	not specified		criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000117039	SCV000337230	benign	not specified	2015-12-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000117039	SCV000519103	likely benign	not specified	2017-10-18	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.
Athena Diagnostics Inc	RCV000711666	SCV000842053	likely benign	not provided	2017-09-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000711666	SCV000885460	likely benign	not provided	2017-12-26	criteria provided, single submitter	clinical testing	Although the FKRP p.Ile274Met variant (rs77138370) has not been reported in the medical literature, it is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.88% in the African population (identified in 127 out of 14,360 chromosomes). This variant is also classified as benign/likely benign in ClinVar (Variant ID: 129058). The isoleucine at codon 274 is moderately conserved considering 11 species (Alamut software v2.10.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: damaging, PolyPhen2: benign, MutationTaster: disease causing). Therefore, based on the available evidence, the p.Ile274Met variant is classified as likely benign.
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.