ClinVar Miner

Submissions for variant NM_005340.7(HINT1):c.110G>C (p.Arg37Pro) (rs149782619)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235535 SCV000293545 pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing The R37P pathogenic variant has been previously reported to segregate with autosomal recessive axonal neuropathy with neuromyotonia in many patients who were either homozygous for the variant or who also had a second variant on the opposite allele (Zimon et al., 2012; Lassuthova et al., 2015; Jerath et al., 2015). Complementation studies in yeast show that the R37P variant does not have residual enzyme activity, suggesting a pathogenic effect (Zimon et al., 2012). It has been reported as a founder mutation in the Czech population, accounting for 95% of pathogenic alleles (Lassuthova et al., 2015). It 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 R37P variant is a non-conservative amino acid substitution, which occurs at a position that is not conserved across species. Based on the currently available information, the R37P variant is interpreted to be pathogenic, and homozygosity for the R37P pathogenic variant is consistent with a diagnosis of a HINT1-related neuropathy
Institute of Human Genetics,Cologne University RCV000030852 SCV000787791 pathogenic Autosomal recessive axonal neuropathy with neuromyotonia 2018-04-25 no assertion criteria provided clinical testing
Invitae RCV000030852 SCV000776537 pathogenic Autosomal recessive axonal neuropathy with neuromyotonia 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 37 of the HINT1 protein (p.Arg37Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is present in population databases (rs149782619, ExAC 0.08%). This variant has been reported in the homozygous or compound heterozygous state in many individuals affected with axonal neuropathy and neuromyotonia and is considered the most common pathogenic mutation in the Czech population (PMID: 22961002, 26182879, 25342199, 27549087). This variant has also been reported to segregate with disease in multiple families (PMID: 22961002, 25342199). ClinVar contains an entry for this variant (Variation ID: 37312). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000030852 SCV000053527 pathogenic Autosomal recessive axonal neuropathy with neuromyotonia 2012-10-01 no assertion criteria provided literature only

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