VCV000037312.70 - ClinVar

NM_005340.7(HINT1):c.110G>C (p.Arg37Pro)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(14)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005340.7(HINT1):c.110G>C (p.Arg37Pro)

Variation ID: 37312 Accession: VCV000037312.70

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q23.3 5: 131165096 (GRCh38) [ NCBI UCSC ] 5: 130500789 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 11, 2015	Nov 24, 2024	Aug 2, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_005340.7:c.110G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005331.1:p.Arg37Pro	missense
NM_005340.5:c.110G>C
NR_024610.3:n.161G>C		non-coding transcript variant
NR_024611.3:n.161G>C		non-coding transcript variant
NR_073488.2:n.161G>C		non-coding transcript variant
NR_134494.2:n.161G>C		non-coding transcript variant
NR_134495.2:n.161G>C		non-coding transcript variant
NC_000005.10:g.131165096C>G
NC_000005.9:g.130500789C>G
NG_032998.1:g.5253G>C
	P49773:p.Arg37Pro

... more HGVS ... less HGVS

Protein change

R37P

Other names

Canonical SPDI

NC_000005.10:131165095:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00026

The Genome Aggregation Database (gnomAD) 0.00064

Trans-Omics for Precision Medicine (TOPMed) 0.00010

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Exome Aggregation Consortium (ExAC) 0.00025

Links

ClinGen: CA130158 UniProtKB: P49773#VAR_069212 OMIM: 601314.0001 dbSNP: rs149782619 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
HINT1		-	-	GRCh38 GRCh37	123	149

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal recessive axonal neuropathy with neuromyotonia	Pathogenic (10)	criteria provided, multiple submitters, no conflicts	Aug 2, 2024	RCV000030852.25
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 1, 2024	RCV000235535.27
Peripheral neuropathy	Pathogenic (1)	criteria provided, single submitter	Jul 10, 2021	RCV001814014.2
Inborn genetic diseases	Pathogenic (1)	criteria provided, single submitter	Nov 23, 2022	RCV002426529.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Sep 06, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002581875.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PM3_VSTR, PS4_MOD, PS3_SUP, PM2_SUP, PP1	Number of individuals with the variant: 3 Sex: female
Pathogenic (Dec 19, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000293545.11 First in ClinVar: Jul 24, 2016 Last updated: Dec 31, 2022	Comment: Published functional studies demonstrate loss of enzyme function in the homozygous state (Zimon et al., 2012); Reported as a founder mutation in the Czech population, … (more) Published functional studies demonstrate loss of enzyme function in the homozygous state (Zimon et al., 2012); Reported as a founder mutation in the Czech population, accounting for 95% of pathogenic alleles (Lassuthova et al., 2015).; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26182879, 32709422, 22961002, 24918641, 25342199, 26194197, 23043279, 27549087, 29787766, 31787464, 31848916, 34562060, 33726816, 34694653, 33663550) (less)
Pathogenic (Nov 14, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV004101800.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Clinical Features: Polyneuropathy (present)
Pathogenic (Dec 29, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000776537.8 First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024	Publications: PubMed (5) PubMed: 28492532‚ 22961002‚ 25342199‚ 26182879‚ 27549087 Comment: This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 37 of the HINT1 protein (p.Arg37Pro). … (more) This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 37 of the HINT1 protein (p.Arg37Pro). This variant is present in population databases (rs149782619, gnomAD 0.09%). This missense change has been observed in individuals with clinical features of distal hereditary motor neuropathy (PMID: 22961002, 25342199, 26182879, 27549087). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 37312). 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. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Aug 02, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia (Autosomal recessive inheritance) Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV005368248.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024	Comment: Criteria applied: PM3_VSTR,PS4_SUP,PM2_SUP Clinical Features: Mild global developmental delay (present) , Myoclonic seizure (present) , Polyneuropathy (present) Sex: male
Pathogenic (Jan 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001245741.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Comment: HINT1: PM3:Very Strong, PP1:Strong, PM2, PS3:Supporting, BP4 Number of individuals with the variant: 11
Pathogenic (Oct 02, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001366390.2 First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020	Comment: This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PP2,PP5.
Pathogenic (Jul 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peripheral neuropathy Affected status: yes Allele origin: germline	Kariminejad - Najmabadi Pathology & Genetics Center Accession: SCV001755654.1 First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022
Pathogenic (Feb 23, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia Affected status: yes Allele origin: unknown	3billion Accession: SCV003841438.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (3) PubMed: 27549087‚ 22961002‚ 26182879 Comment: The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.030%). Missense changes are a common disease-causing mechanism. … (more) The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.030%). Missense changes are a common disease-causing mechanism. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000037312). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 4 similarly affected unrelated individuals (PMID: 22961002, 22961002, 26182879, 27549087). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less) Clinical Features: Muscle spasm (present) , Hyperkinetic movements (present) , Paresthesia (present) , Distal lower limb muscle weakness (present) , Limb ataxia (present) , Hypotrophy of the … (more) Muscle spasm (present) , Hyperkinetic movements (present) , Paresthesia (present) , Distal lower limb muscle weakness (present) , Limb ataxia (present) , Hypotrophy of the small hand muscles (present) , Distal upper limb muscle weakness (present) , Proximal muscle weakness in lower limbs (present) , Impaired vibratory sensation (present) , Steppage gait (present) , Absent Achilles reflex (present) , Achilles tendon contracture (present) (less)
Pathogenic (Jun 23, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV004236170.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024
Pathogenic (Nov 23, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002742689.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (5) PubMed: 22961002‚ 25342199‚ 26182879‚ 29787766‚ 31848916 Comment: The c.110G>C (p.R37P) alteration is located in exon 1 (coding exon 1) of the HINT1 gene. This alteration results from a G to C substitution … (more) The c.110G>C (p.R37P) alteration is located in exon 1 (coding exon 1) of the HINT1 gene. This alteration results from a G to C substitution at nucleotide position 110, causing the arginine (R) at amino acid position 37 to be replaced by a proline (P). Based on data from the Genome Aggregation Database (gnomAD), the HINT1 c.110G>C alteration was observed in 0.03% (85/281,678) of total alleles studied. The p.R37P alteration, one of three founder mutations and considered to be the most common, has been reported in homozygous and compound heterozygous individuals with autosomal recessive axonal neuropathy with neuromyotonia (Zimo, 2012; La&scaron;&scaron;uthová, 2015; Jerath, 2015; Shchagina, 2020). This amino acid position is poorly conserved in available vertebrate species. Protein contain p.R37P fails to form functional dimers and exists as monomers, which showed significant loss of secondary structure compared to wild type and showed reduced near UV-absorption indicating incorrect or improper folding (Shah, 2018). This alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Neuberg Centre For Genomic Medicine, NCGM Accession: SCV005400845.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Comment: The observed missense c.110G>C (p.Arg37Pro) variant in HINT1 gene has been reported previously in homozygous and compound heterozygous states in multiple individuals affected with neuromyotonia … (more) The observed missense c.110G>C (p.Arg37Pro) variant in HINT1 gene has been reported previously in homozygous and compound heterozygous states in multiple individuals affected with neuromyotonia and axonal neuropathy (Zimon et al., 2012; Laššuthová et al., 2015; Jerath et al., 2015; Laššuthová et al., 2016). It has also been observed to segregate with disease in related individuals. Functional studies demonstrate this variant to cause loss of enzyme function (Zimon et al., 2012). This variant is present with allele frequency of 0.03% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic (multiple submissions). Computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Arg37Pro in HINT1 is predicted as conserved by PhyloP across 100 vertebrates. The amino acid Arg at position 37 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Apr 25, 2018)	no assertion criteria provided Method: clinical testing	Autosomal recessive axonal neuropathy with neuromyotonia Affected status: yes Allele origin: germline	Institute of Human Genetics, Cologne University Accession: SCV000787791.1 First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015
Pathogenic (Oct 01, 2012)	no assertion criteria provided Method: literature only	NEUROMYOTONIA AND AXONAL NEUROPATHY, AUTOSOMAL RECESSIVE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000053527.4 First in ClinVar: Apr 04, 2013 Last updated: Nov 11, 2023	Publications: PubMed (2) PubMed: 22961002‚ 34694653 Comment on evidence: In 2 Belgian sibs with autosomal recessive neuromyotonia and axonal neuropathy (NMAN; 137200), Zimon et al. (2012) identified compound heterozygosity for 2 mutations in the … (more) In 2 Belgian sibs with autosomal recessive neuromyotonia and axonal neuropathy (NMAN; 137200), Zimon et al. (2012) identified compound heterozygosity for 2 mutations in the HINT1 gene: a 110G-C transversion in exon 1, resulting in an arg37-to-pro (R37P) substitution at a nonconserved residue, and a 250T-C transition in exon 3, resulting in a cys84-to-arg (C84R; 601314.0002) substitution at a relatively conserved residue close to the dimer interface important for enzyme activity. The mutations were found by linkage analysis and whole-genome sequencing; neither mutation was found in 270 Belgian controls. C84R was not found in 885 additional controls. In an independent study, linkage analysis and exome sequencing of a consanguineous Austrian family with a similar disorder identified homozygosity for the R37P mutation in 3 affected sibs. Subsequent analysis of this gene in larger cohorts identified 21 additional families who were homozygous for the R37P mutation. The 110G-C change has been reported as a polymorphism (rs149782619), and was heterozygous in 3 of 200 Serbian control individuals. It was also found in 1 of 7,019 European control alleles and in 1 of 3,737 African American control alleles from large exome databases. Haplotype analysis indicated a founder effect for both R37P and C84R. The phenotype was characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. Affected individuals also had action myotonia in the hands and/or neuromyotonic discharges on needle EMG. Heterozygous mutation carriers were unaffected. Complementation studies in yeast showed that the R37P mutant enzyme had no residual activity, whereas the C84R mutant had some residual enzyme activity. Patient lymphoblasts with the R37P and/or C84R mutations showed normal HINT1 mRNA levels, but negligible HINT1 protein expression, suggesting posttranslational degradation. The pathogenic mechanism is thus a loss of function. Zimon et al. (2012) commented that since R37P is predicted to be a benign variant and is found in controls, it could have been discarded during data filtering. However, functional data supported the pathogenicity of the variant in homozygous state. Kontogeorgiou et al. (2021) identified 4 Greek patients with NMAN with R37P mutations, 2 in homozygosity (patients 2 and 3) and 2 in compound heterozygosity (patients 1 and 4) with the C84R mutation (601314.0002). (less)
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Comment:

Published functional studies demonstrate loss of enzyme function in the homozygous state (Zimon et al., 2012); Reported as a founder mutation in the Czech population, accounting for 95% of pathogenic alleles (Lassuthova et al., 2015).; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26182879, 32709422, 22961002, 24918641, 25342199, 26194197, 23043279, 27549087, 29787766, 31787464, 31848916, 34562060, 33726816, 34694653, 33663550)

Comment:

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 37 of the HINT1 protein (p.Arg37Pro). This variant is present in population databases (rs149782619, gnomAD 0.09%). This missense change has been observed in individuals with clinical features of distal hereditary motor neuropathy (PMID: 22961002, 25342199, 26182879, 27549087). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 37312). 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. For these reasons, this variant has been classified as Pathogenic.

Comment:

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.030%). Missense changes are a common disease-causing mechanism. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000037312). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 4 similarly affected unrelated individuals (PMID: 22961002, 22961002, 26182879, 27549087). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

The c.110G>C (p.R37P) alteration is located in exon 1 (coding exon 1) of the HINT1 gene. This alteration results from a G to C substitution at nucleotide position 110, causing the arginine (R) at amino acid position 37 to be replaced by a proline (P). Based on data from the Genome Aggregation Database (gnomAD), the HINT1 c.110G>C alteration was observed in 0.03% (85/281,678) of total alleles studied. The p.R37P alteration, one of three founder mutations and considered to be the most common, has been reported in homozygous and compound heterozygous individuals with autosomal recessive axonal neuropathy with neuromyotonia (Zimo, 2012; La&scaron;&scaron;uthová, 2015; Jerath, 2015; Shchagina, 2020). This amino acid position is poorly conserved in available vertebrate species. Protein contain p.R37P fails to form functional dimers and exists as monomers, which showed significant loss of secondary structure compared to wild type and showed reduced near UV-absorption indicating incorrect or improper folding (Shah, 2018). This alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

Comment:

The observed missense c.110G>C (p.Arg37Pro) variant in HINT1 gene has been reported previously in homozygous and compound heterozygous states in multiple individuals affected with neuromyotonia and axonal neuropathy (Zimon et al., 2012; Laššuthová et al., 2015; Jerath et al., 2015; Laššuthová et al., 2016). It has also been observed to segregate with disease in related individuals. Functional studies demonstrate this variant to cause loss of enzyme function (Zimon et al., 2012). This variant is present with allele frequency of 0.03% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic (multiple submissions). Computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Arg37Pro in HINT1 is predicted as conserved by PhyloP across 100 vertebrates. The amino acid Arg at position 37 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
HINT1-related neuropathy in Greek patients with Charcot-Marie-Tooth disease.	Kontogeorgiou Z	Journal of the peripheral nervous system : JPNS	2021	PMID: 34694653
HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients.	Shchagina OA	Molecular biology reports	2020	PMID: 31848916
Structure and Functional Characterization of Human Histidine Triad Nucleotide-Binding Protein 1 Mutations Associated with Inherited Axonal Neuropathy with Neuromyotonia.	Shah RM	Journal of molecular biology	2018	PMID: 29787766
Improving diagnosis of inherited peripheral neuropathies through gene panel analysis.	Laššuthová P	Orphanet journal of rare diseases	2016	PMID: 27549087
A case of neuromyotonia and axonal motor neuropathy: A report of a HINT1 mutation in the United States.	Jerath NU	Muscle & nerve	2015	PMID: 26182879
Mutations in HINT1 are one of the most frequent causes of hereditary neuropathy among Czech patients and neuromyotonia is rather an underdiagnosed symptom.	Laššuthová P	Neurogenetics	2015	PMID: 25342199
Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.	Zimoń M	Nature genetics	2012	PMID: 22961002

Text-mined citations for rs149782619 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_005340.7(HINT1):c.110G>C (p.Arg37Pro)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs149782619 ...