Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523424 | SCV000618637 | uncertain significance | not provided | 2022-03-15 | criteria provided, single submitter | clinical testing | Reported in an individual with a long history of muscle cramps who also harbored additional variants in other neuropathy-related genes; a second HINT1 variant was not identified (Peddareddygari et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: Peddareddygari2021[ARTICLE]) |
Invitae | RCV001210096 | SCV001381563 | uncertain significance | Autosomal recessive axonal neuropathy with neuromyotonia | 2021-01-29 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs780156681, ExAC 0.002%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with HINT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 450095). This sequence change replaces histidine with leucine at codon 122 of the HINT1 protein (p.His122Leu). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and leucine. |
Ambry Genetics | RCV002456006 | SCV002613991 | uncertain significance | Inborn genetic diseases | 2021-06-12 | criteria provided, single submitter | clinical testing | The p.H122L variant (also known as c.365A>T), located in coding exon 3 of the HINT1 gene, results from an A to T substitution at nucleotide position 365. The histidine at codon 122 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. 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. |