ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.1664G>T (p.Ser555Ile) (rs375014127)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000498271 SCV000339889 uncertain significance not provided 2018-08-30 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414780 SCV000492898 likely pathogenic Myopathy 2014-12-12 criteria provided, single submitter clinical testing
GeneDx RCV000498271 SCV000589776 uncertain significance not provided 2018-11-07 criteria provided, single submitter clinical testing The S555I variant was previously reported in an individual with LGMD, who harbored an additional pathogenic variant on the other ANO5 allele (in trans); however, functional studies where not performed (Kuhn et al., 2016). The S555I variant is observed in 25/126546 (0.02%) alleles from individuals of European background (Lek et al., 2016). The S555I 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000627020 SCV000747723 pathogenic Elevated serum creatine phosphokinase; Distal muscle weakness; Fatty replacement of skeletal muscle 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001068054 SCV001233143 uncertain significance Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces serine with isoleucine at codon 555 of the ANO5 protein (p.Ser555Ile). The serine residue is moderately conserved and there is a large physicochemical difference between serine and isoleucine. This variant is present in population databases (rs375014127, ExAC 0.02%). This variant has been observed in combination with other ANO5 variants in individuals with limb-girdle muscular dystrophy (PMID: 25891276, 26886200, 27911336, 30564623). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 286450). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198354 SCV001369258 pathogenic Gnathodiaphyseal dysplasia 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PM3,PP4,PP5.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000498271 SCV001446406 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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.