VCV000005903.48 - ClinVar

NM_000334.4(SCN4A):c.3917G>T (p.Gly1306Val)

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.

(10)

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_000334.4(SCN4A):c.3917G>T (p.Gly1306Val)

Variation ID: 5903 Accession: VCV000005903.48

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q23.3 17: 63943846 (GRCh38) [ NCBI UCSC ] 17: 62021206 (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	Feb 13, 2015	Oct 20, 2024	Aug 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000334.4:c.3917G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000325.4:p.Gly1306Val	missense
NC_000017.11:g.63943846C>A
NC_000017.10:g.62021206C>A
NG_011699.1:g.34073G>T
NG_042788.1:g.26754C>A
	P35499:p.Gly1306Val

... more HGVS ... less HGVS

Protein change

G1306V

Other names

Canonical SPDI

NC_000017.11:63943845:C:A

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.

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

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

ClinGen: CA117840 UniProtKB: P35499#VAR_001569 OMIM: 603967.0007 dbSNP: rs80338792 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.
GH-LCR	-	-	-	GRCh38	-	1626
SCN4A		-	-	GRCh38 GRCh37	736	2045

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.
Paramyotonia congenita of Von Eulenburg	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Feb 23, 2023	RCV000006264.13
Potassium-aggravated myotonia	Pathogenic (1)	no assertion criteria provided	May 1, 2009	RCV000006265.10
not provided	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Jul 1, 2023	RCV000479620.35
Familial hyperkalemic periodic paralysis	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Aug 11, 2023	RCV000690377.12
SCN4A-related non-dystrophic myotonia	Pathogenic (1)	no assertion criteria provided	Apr 6, 2022	RCV002267601.3

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 (Jan 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial hyperkalemic periodic paralysis Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001370154.2 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: PS1,PS3,PM2,PP2,PP3.
Pathogenic (Oct 25, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paramyotonia congenita of Von Eulenburg Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002581212.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PS3, PS2_MOD, PS4_MOD, PM1, PM5, PM2_SUP, PP1, PP3	Number of individuals with the variant: 1 Sex: male
Pathogenic (May 13, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000567468.4 First in ClinVar: Apr 27, 2017 Last updated: Apr 17, 2019	Comment: Reported previously as a heterozygous variant in two unrelated families with paramyotonia congenita (McClatchey et al., 1992); Functional studies suggest that G1306V results in slower … (more) Reported previously as a heterozygous variant in two unrelated families with paramyotonia congenita (McClatchey et al., 1992); Functional studies suggest that G1306V results in slower inactivation of the SCN4A sodium channel (Lerche et al., 1993); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 8308722, 1310898, 27415035, 26944947, 18337100, 18337730, 28150151, 26885337, 26080010, 22094069, 20445432, 17823953, 16832098, 8044656, 16392038, 7473241, 32849172, 32660787) (less)
Pathogenic (Feb 23, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paramyotonia congenita of Von Eulenburg Affected status: yes Allele origin: unknown	3billion Accession: SCV003841909.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (1) PubMed: 27415035 Comment: The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). 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: <0.001%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.92; 3Cnet: 0.91). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000005903). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 27415035). Different missense changes at the same codon (p.Gly1306Ala, p.Gly1306Glu) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000005908, VCV000005920). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less) Clinical Features: Myalgia (present) , Fasciculations (present) , Limb fasciculations (present) , Elevated circulating creatine kinase concentration (present) , Fatigue (present) , Somatic sensory dysfunction (present) , … (more) Myalgia (present) , Fasciculations (present) , Limb fasciculations (present) , Elevated circulating creatine kinase concentration (present) , Fatigue (present) , Somatic sensory dysfunction (present) , EMG: myotonic runs (present) , Hand tremor (present) , Esodeviation (present) , Weakness of facial musculature (present) , Calf muscle hypertrophy (present) , Proximal muscle weakness (present) (less)
Pathogenic (May 03, 2023)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV000615092.4 First in ClinVar: Apr 27, 2017 Last updated: Jan 26, 2024	Publications: PubMed (13) PubMed: 28150151‚ 27415035‚ 8044656‚ 7473241‚ 1310898‚ 8308722‚ 32849172‚ 20445432‚ 18337730‚ 33263785‚ 16786525‚ 32660787‚ 16392038 Comment: The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant associates with paramyotonia congenita in multiple families, and is … (more) The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant associates with paramyotonia congenita in multiple families, and is reported in multiple other unrelated individuals with non-dystrophic myotonia. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function. Multiple studies indicate that this variant disrupts normal ion channel properties, resulting in aberrant channel regulation of current and signaling (PMID: 7473241, 16392038). (less)
Pathogenic (Aug 11, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Familial hyperkalemic periodic paralysis Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000818060.7 First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024	Publications: PubMed (20) PubMed: 28492532‚ 1310898‚ 8044656‚ 8308722‚ 17823953‚ 18337100‚ 18337730‚ 20445432‚ 22094069‚ 27415035‚ 7473241‚ 16392038‚ 7980103‚ 16832098‚ 20713951‚ 25088311‚ 25311598‚ 26080010‚ 26885337‚ 26944947 Comment: This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1306 of the SCN4A protein (p.Gly1306Val). … (more) This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1306 of the SCN4A protein (p.Gly1306Val). This variant is present in population databases (rs80338792, gnomAD 0.0009%). This missense change has been observed in individuals with paramyotonia congenita (PMID: 1310898, 8044656, 8308722, 17823953, 18337100, 18337730, 20445432, 22094069, 27415035). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5903). 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 SCN4A protein function. Experimental studies have shown that this missense change affects SCN4A function (PMID: 7473241, 16392038). This variant disrupts the p.Gly1306 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7980103, 16832098, 20713951, 25088311, 25311598, 26080010, 26885337, 26944947). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Jul 01, 2023)	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: SCV001249362.26 First in ClinVar: May 09, 2020 Last updated: Oct 20, 2024	Comment: SCN4A: PM2, PM5, PP1:Moderate, PS4:Moderate, PP3, PS3:Supporting Number of individuals with the variant: 5
Pathogenic (Apr 06, 2022)	no assertion criteria provided Method: research	SCN4A-related non-dystrophic myotonia Affected status: yes Allele origin: germline	Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Accession: SCV002549812.1 First in ClinVar: Jul 23, 2022 Last updated: Jul 23, 2022
Pathogenic (May 01, 2009)	no assertion criteria provided Method: literature only	PARAMYOTONIA CONGENITA Affected status: not provided Allele origin: germline	OMIM Accession: SCV000026446.5 First in ClinVar: Apr 04, 2013 Last updated: Jul 23, 2024	Publications: PubMed (3) PubMed: 1310898‚ 8308722‚ 18337100 Comment on evidence: In a Belgian family with paramyotonia congenita (PMC; 168300), McClatchey et al. (1992) identified a heterozygous c.3917G-T transversion in the SCN4A gene, resulting in a … (more) In a Belgian family with paramyotonia congenita (PMC; 168300), McClatchey et al. (1992) identified a heterozygous c.3917G-T transversion in the SCN4A gene, resulting in a gly1306-to-val (G1306V) substitution. The mutation affected a highly conserved residue in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Muscle weakness was not reported. The authors suggested that this is a temperature-sensitive mutation. Lerche et al. (1993) identified a heterozygous G1306V substitution in a mother and son with potassium-aggravated myotonia (608390). Muscle stiffness in these individuals was also aggravated by exercise, but not by cold. Muscle weakness was not reported. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. Lerche et al. (1993) identified different pathogenic mutations in the same codon (G1306A; 603967.0012 and G1306E; 603967.0025) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. Dupre et al. (2009) reported French Canadian patients with myotonia associated with the G1306V mutation. They had moderate myotonia with mild muscle hypertrophy. They noted exacerbation of symptoms with cold temperatures but no paradoxical myotonia. Female patients showed dramatic symptom improvement after menopause. (less)
Pathogenic (May 01, 2009)	no assertion criteria provided Method: literature only	MYOTONIA, POTASSIUM-AGGRAVATED Affected status: not provided Allele origin: germline	OMIM Accession: SCV000026447.5 First in ClinVar: Apr 04, 2013 Last updated: Jul 23, 2024	Publications: PubMed (3) PubMed: 1310898‚ 8308722‚ 18337100 Comment on evidence: In a Belgian family with paramyotonia congenita (PMC; 168300), McClatchey et al. (1992) identified a heterozygous c.3917G-T transversion in the SCN4A gene, resulting in a … (more) In a Belgian family with paramyotonia congenita (PMC; 168300), McClatchey et al. (1992) identified a heterozygous c.3917G-T transversion in the SCN4A gene, resulting in a gly1306-to-val (G1306V) substitution. The mutation affected a highly conserved residue in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Muscle weakness was not reported. The authors suggested that this is a temperature-sensitive mutation. Lerche et al. (1993) identified a heterozygous G1306V substitution in a mother and son with potassium-aggravated myotonia (608390). Muscle stiffness in these individuals was also aggravated by exercise, but not by cold. Muscle weakness was not reported. Patch-clamp recordings on patient muscle samples showed slower sodium fast channel inactivation and an increase in late channel opening, resulting in a steady-state inward current, sustained muscle depolarization, and muscle fiber hyperexcitability. Lerche et al. (1993) identified different pathogenic mutations in the same codon (G1306A; 603967.0012 and G1306E; 603967.0025) in other families with similar disorders, indicating that residue 1306 is important for sodium channel inactivation. Dupre et al. (2009) reported French Canadian patients with myotonia associated with the G1306V mutation. They had moderate myotonia with mild muscle hypertrophy. They noted exacerbation of symptoms with cold temperatures but no paradoxical myotonia. Female patients showed dramatic symptom improvement after menopause. (less)

Comment:

Reported previously as a heterozygous variant in two unrelated families with paramyotonia congenita (McClatchey et al., 1992); Functional studies suggest that G1306V results in slower inactivation of the SCN4A sodium channel (Lerche et al., 1993); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 8308722, 1310898, 27415035, 26944947, 18337100, 18337730, 28150151, 26885337, 26080010, 22094069, 20445432, 17823953, 16832098, 8044656, 16392038, 7473241, 32849172, 32660787)

Comment:

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.92; 3Cnet: 0.91). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000005903). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 27415035). Different missense changes at the same codon (p.Gly1306Ala, p.Gly1306Glu) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000005908, VCV000005920). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant associates with paramyotonia congenita in multiple families, and is reported in multiple other unrelated individuals with non-dystrophic myotonia. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function. Multiple studies indicate that this variant disrupts normal ion channel properties, resulting in aberrant channel regulation of current and signaling (PMID: 7473241, 16392038).

Comment:

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1306 of the SCN4A protein (p.Gly1306Val). This variant is present in population databases (rs80338792, gnomAD 0.0009%). This missense change has been observed in individuals with paramyotonia congenita (PMID: 1310898, 8044656, 8308722, 17823953, 18337100, 18337730, 20445432, 22094069, 27415035). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5903). 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 SCN4A protein function. Experimental studies have shown that this missense change affects SCN4A function (PMID: 7473241, 16392038). This variant disrupts the p.Gly1306 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7980103, 16832098, 20713951, 25088311, 25311598, 26080010, 26885337, 26944947). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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
Non-dystrophic myotonias: clinical and mutation spectrum of 70 German patients.	Vereb N	Journal of neurology	2021	PMID: 33263785
Clinical and Molecular Spectrum of Myotonia and Periodic Paralyses Associated With Mutations in SCN4A in a Large Cohort of Italian Patients.	Maggi L	Frontiers in neurology	2020	PMID: 32849172
Mutation spectrum and health status in skeletal muscle channelopathies in Japan.	Sasaki R	Neuromuscular disorders : NMD	2020	PMID: 32660787
Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.	Huang W	Protein & cell	2017	PMID: 28150151
Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature.	Yang X	Channels (Austin, Tex.)	2017	PMID: 27415035
Flecainide-Responsive Myotonia Permanens With SNEL Onset: A New Case and Literature Review.	Portaro S	Pediatrics	2016	PMID: 26944947
Mutation analysis in exons 22 and 24 of SCN4A gene in Iranian patients with non-dystrophic myotonia.	Heidari MM	Iranian journal of neurology	2015	PMID: 26885337
Painful cramps and giant myotonic discharges in a family with the Nav1.4-G1306A mutation.	Torbergsen T	Muscle & nerve	2015	PMID: 26080010
Mutations in SCN4A: a rare but treatable cause of recurrent life-threatening laryngospasm.	Singh RR	Pediatrics	2014	PMID: 25311598
Heterozygous CLCN1 mutations can modulate phenotype in sodium channel myotonia.	Furby A	Neuromuscular disorders : NMD	2014	PMID: 25088311
Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene.	Mazón MJ	Neuromuscular disorders : NMD	2012	PMID: 22094069
Severe neonatal episodic laryngospasm due to de novo SCN4A mutations: a new treatable disorder.	Lion-Francois L	Neurology	2010	PMID: 20713951
A case of paramyotonia congenita without periodic paralysis: electrophysiological and molecular genetic studies.	Park JH	The neurologist	2010	PMID: 20445432
Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.	Dupré N	Neuromuscular disorders : NMD	2009	PMID: 18337100
In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in families with non-dystrophic myotonia.	Trip J	European journal of human genetics : EJHG	2008	PMID: 18337730
Reduced muscle-fiber conduction but normal slowing after cold exposure in paramyotonia congenita.	Blijham PJ	Muscle & nerve	2008	PMID: 17823953
Autosomal dominant monosymptomatic myotonia permanens.	Colding-Jørgensen E	Neurology	2006	PMID: 16832098
Cold extends electromyography distinction between ion channel mutations causing myotonia.	Fournier E	Annals of neurology	2006	PMID: 16786525
K-aggravated myotonia mutations at residue G1306 differentially alter deactivation gating of human skeletal muscle sodium channels.	Groome JR	Cellular and molecular neurobiology	2005	PMID: 16392038
Different effects on gating of three myotonia-causing mutations in the inactivation gate of the human muscle sodium channel.	Mitrović N	The Journal of physiology	1995	PMID: 7473241
Mutations in the muscle sodium channel gene (SCN4A) in 13 French families with hyperkalemic periodic paralysis and paramyotonia congenita: phenotype to genotype correlations and demonstration of the predominance of two mutations.	Plassart E	European journal of human genetics : EJHG	1994	PMID: 8044656
Myotonia fluctuans. A third type of muscle sodium channel disease.	Ricker K	Archives of neurology	1994	PMID: 7980103
Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.	Lerche H	The Journal of physiology	1993	PMID: 8308722
Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.	McClatchey AI	Cell	1992	PMID: 1310898
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Text-mined citations for rs80338792 ...

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Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_000334.4(SCN4A):c.3917G>T (p.Gly1306Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80338792 ...