ClinVar Miner

Submissions for variant NM_000843.4(GRM6):c.1214T>C (p.Ile405Thr)

gnomAD frequency: 0.00003  dbSNP: rs121434304
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000439410 SCV000231579 likely pathogenic not provided 2017-06-13 criteria provided, single submitter clinical testing
GeneDx RCV000439410 SCV000521174 likely pathogenic not provided 2017-01-26 criteria provided, single submitter clinical testing The I405T variant in the GRM6 gene has been reported previously in association with autosomal recessive congenital stationary night blindness when present in the homozygous state (Zeitz et al., 2007). The I405T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I405T 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 addition, this substitution occurs at a position that is conserved across species. Functional studies of the I405T variant demonstrate a transport defect of the GRM6 protein (Zeitz et al., 2007). The I405T variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000439410 SCV002180976 uncertain significance not provided 2023-06-30 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. Experimental studies have shown that this missense change affects GRM6 function (PMID: 17405131). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GRM6 protein function. ClinVar contains an entry for this variant (Variation ID: 5847). This missense change has been observed in individual(s) with congenital stationary night blindness (PMID: 17405131). This variant is present in population databases (rs121434304, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 405 of the GRM6 protein (p.Ile405Thr).
OMIM RCV000006204 SCV000026386 pathogenic Congenital stationary night blindness 1B 2007-08-01 no assertion criteria provided literature only

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.