Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000439410 | SCV000231579 | likely pathogenic | not provided | 2017-06-13 | criteria provided, single submitter | clinical testing | |
Gene |
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 |