ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.1331G>A (p.Arg444His)

gnomAD frequency: 0.00001  dbSNP: rs758736387
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519422 SCV000621277 uncertain significance not provided 2017-10-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POMT1 gene. The R466H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R466H variant is not observed in large population cohorts (Lek et al., 2016). The R466H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001853681 SCV002317078 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy 2020-11-10 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 452467). This variant is present in population databases (rs758736387, ExAC 0.006%). This sequence change replaces arginine with histidine at codon 466 of the POMT1 protein (p.Arg466His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine.

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.