ClinVar Miner

Submissions for variant NM_004737.6(LARGE1):c.211G>A (p.Glu71Lys) (rs116164106)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000710160 SCV000613996 uncertain significance not provided 2017-09-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000710160 SCV000230242 uncertain significance not provided 2016-05-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765632 SCV000896960 uncertain significance Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B6; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A6 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000710160 SCV000582521 uncertain significance not provided 2018-12-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the LARGE gene. The E71K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E71K variant is observed in 69/64,568 (0.1%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E71K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000146258 SCV000193512 uncertain significance Muscular dystrophy 2013-12-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000339092 SCV000438178 uncertain significance Congenital Muscular Dystrophy, alpha-dystroglycan related 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000379599 SCV000438179 uncertain significance Walker-Warburg Syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000555307 SCV000638993 uncertain significance Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B6 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 71 of the LARGE11 protein (p.Glu71Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs116164106, ExAC 0.1%). This variant has not been reported in the literature in individuals with LARGE11-related disease. ClinVar contains an entry for this variant (Variation ID: 158807). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.