Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236287 | SCV000294124 | uncertain significance | not provided | 2016-04-07 | criteria provided, single submitter | clinical testing | The D68V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D68V variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The D68V 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. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000549355 | SCV000658507 | uncertain significance | Autosomal recessive axonal neuropathy with neuromyotonia | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 246535). This variant has not been reported in the literature in individuals affected with HINT1-related conditions. This variant is present in population databases (rs371048016, gnomAD 0.008%). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 68 of the HINT1 protein (p.Asp68Val). |
Ambry Genetics | RCV002418049 | SCV002719732 | uncertain significance | Inborn genetic diseases | 2021-04-05 | criteria provided, single submitter | clinical testing | The p.D68V variant (also known as c.203A>T), located in coding exon 2 of the HINT1 gene, results from an A to T substitution at nucleotide position 203. The aspartic acid at codon 68 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |