Submissions for variant NM_001130987.2(DYSF):c.5276G>A (p.Arg1759His) (rs147678255)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000711566	SCV000334615	uncertain significance	not provided	2015-09-01	criteria provided, single submitter	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000660419	SCV000782506	uncertain significance	Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Myopathy, distal, with anterior tibial onset	2016-11-04	criteria provided, single submitter	clinical testing
Invitae	RCV000689268	SCV000816910	uncertain significance	Qualitative or quantitative defects of dysferlin	2018-12-21	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with histidine at codon 1720 of the DYSF protein (p.Arg1720His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs147678255, ExAC 0.01%). This variant has not been reported in the literature in individuals with DYSF-related disease. ClinVar contains an entry for this variant (Variation ID: 282885). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Athena Diagnostics Inc	RCV000711566	SCV000841945	uncertain significance	not provided	2018-03-26	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000689268	SCV001298484	uncertain significance	Qualitative or quantitative defects of dysferlin	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Natera, Inc.	RCV001274852	SCV001459369	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-01-17	no assertion criteria provided	clinical testing