ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.749A>G (p.Tyr250Cys) (rs781734224)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000364651 SCV000339522 uncertain significance not provided 2016-08-15 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV000663412 SCV000786700 uncertain significance Limb-girdle muscular dystrophy, type 2L criteria provided, single submitter research The heterozygous p.Tyr250Cys variant was identified in the compound heterozygous state by our study in one individual with Limb-Girdle Muscular Dystrophy. The p.Tyr250Cys variant has been reported as a VUS in 2 individuals in ClinVar (ID: 286191). It has also been identified in 0.01% (1/10378) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). The Tyrosine (Tyr) at position 250 is not conserved in mammals or evolutionary distant species, raising the possibility/supporting that a change at this position may be tolerated. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Tyr250Cys variant is uncertain.
Invitae RCV000792580 SCV000931885 uncertain significance Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2019-08-23 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 250 of the ANO5 protein (p.Tyr250Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs781734224, ExAC 0.01%). This variant has not been reported in the literature in individuals with ANO5-related disease. ClinVar contains an entry for this variant (Variation ID: 286191). 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 disruptive, 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.