ClinVar Genomic variation as it relates to human health
NM_020451.3(SELENON):c.943G>A (p.Gly315Ser)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020451.3(SELENON):c.943G>A (p.Gly315Ser)
Variation ID: 4496 Accession: VCV000004496.59
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p36.11 1: 25809753 (GRCh38) [ NCBI UCSC ] 1: 26136244 (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 May 3, 2013 Apr 15, 2024 Feb 5, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_020451.3:c.943G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_065184.2:p.Gly315Ser missense NM_206926.2:c.841G>A NP_996809.1:p.Gly281Ser missense NC_000001.11:g.25809753G>A NC_000001.10:g.26136244G>A NG_009930.1:g.14578G>A LRG_857:g.14578G>A LRG_857t1:c.943G>A LRG_857p1:p.Gly315Ser Q9NZV5:p.Gly315Ser - Protein change
- G315S, G281S
- Other names
- NM_020451.3(SELENON):c.943G>A
- Canonical SPDI
- NC_000001.11:25809752:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe 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.
Exome Aggregation Consortium (ExAC) 0.00017
The Genome Aggregation Database (gnomAD), exomes 0.00018
Trans-Omics for Precision Medicine (TOPMed) 0.00029
The Genome Aggregation Database (gnomAD) 0.00030
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 | ||
---|---|---|---|---|---|---|
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. |
|||
SELENON | - | - |
GRCh38 GRCh37 |
692 | 703 |
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. |
---|---|---|---|---|
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Jan 16, 2024 | RCV000004753.33 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Dec 3, 2019 | RCV000004754.23 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Sep 18, 2023 | RCV000082020.41 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 29, 2021 | RCV000681664.16 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 16, 2018 | RCV000778235.12 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Mar 30, 2021 | RCV003224794.8 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 5, 2024 | RCV003993737.1 |
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
(Dec 24, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000232288.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 5
Sex: mixed
|
|
Pathogenic
(Jun 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Eichsfeld type congenital muscular dystrophy
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000967683.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Gly315Ser variant in SEPN1 has been reported in 8 individuals with a conge nital myopathy, including 6 who were homozygous and 2 compound heterozygous … (more)
The p.Gly315Ser variant in SEPN1 has been reported in 8 individuals with a conge nital myopathy, including 6 who were homozygous and 2 compound heterozygous with another pathogenic allele (Ferreiro 2002, Clarke 2006, Maiti 2009, Maggi 2013), and segregated in 5 affected relatives (Ferreiro 2002, Clarke 2006). This varia nt has been identified in 0.04% (50/126676) of European chromosomes by the Genom e Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121908 188) and in ClinVar (Variation ID: 4496). Although this variant has been seen i n the general population, its frequency is low enough to be consistent with a re cessive carrier frequency. Computational prediction tools and conservation analy sis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Additionally, analysis using fibroblast cells of an affected patient showed an impact on protein activity (Ma iti 2009). In summary, this variant is pathogenic for congenital muscular dystro phy with spinal rigidity in an autosomal recessive manner. ACMG/AMP Criteria app lied: PM3_Strong; PP1_Strong; PP3. (less)
Number of individuals with the variant: 1
|
|
Pathogenic
(Jun 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Eichsfeld type congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020053.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Dec 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Eichsfeld type congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004240986.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
Variant summary: SELENON c.943G>A (p.Gly315Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: SELENON c.943G>A (p.Gly315Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 249510 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SELENON causing Eichsfeld Type Congenital Muscular Dystrophy (0.00018 vs 0.0011), allowing no conclusion about variant significance. c.943G>A has been reported in the literature as biallelic homozygous or compound heterozygous genotypes in multiple individuals affected with features of Eichsfeld Type Congenital Muscular Dystrophy (example, Ferreiro_2004, Nicolau_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15122708, 17204937, 31321302). Multiple submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(Jan 16, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Eichsfeld type congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000634423.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 315 of the SELENON protein (p.Gly315Ser). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 315 of the SELENON protein (p.Gly315Ser). This variant is present in population databases (rs121908188, gnomAD 0.04%). This missense change has been observed in individual(s) with SELENON-related conditions (PMID: 12192640, 16365872, 17951086, 23394784; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4496). 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 SELENON protein function. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246685.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
SELENON-related myopathy
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812522.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
This sequence change in SELENON is predicted to replace glycine with serine at codon 315, p.(Gly315Ser). The glycine residue is highly conserved (100 vertebrates, Multiz … (more)
This sequence change in SELENON is predicted to replace glycine with serine at codon 315, p.(Gly315Ser). The glycine residue is highly conserved (100 vertebrates, Multiz Alignments). There is a small physicochemical difference between glycine and serine. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.07% (791/1,180,030 alleles, 1 homozygote) in the European (non-Finnish) population. This variant has been detected in the homozygous and compound heterozygous state in multiple individuals with myopathy (confirmed in trans pathogenic variant in at least one individual) and segregates with disease in multiple families (PMID: 12192640, 16365872, 30932294). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.949). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PM3_VeryStrong, PP1_Strong, PP3_Moderate. (less)
|
|
Pathogenic
(Jul 08, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics Inc
Accession: SCV000843765.1
First in ClinVar: Oct 19, 2018 Last updated: Oct 19, 2018 |
|
|
Pathogenic
(Oct 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
SEPN1-Related Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000914403.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
Across a selection of available literature, the SEPN1 c.943G>A (p.Gly315Ser) missense variant has been identified in a homozygous state in 12 individuals and in a … (more)
Across a selection of available literature, the SEPN1 c.943G>A (p.Gly315Ser) missense variant has been identified in a homozygous state in 12 individuals and in a compound heterozygous state in four individuals from a total of ten unrelated families, with phenotypes including multiminicore disease, rigid spine muscular dystrophy, congenital fiber-type disproportion, and nemaline myopathy (Ferreiro et al. 2002; Venance et al. 2005; Clarke et al. 2006; Schara et al. 2008; Maggi et al. 2013). The variant was absent from 400 controls but is reported at a frequency of 0.00059 in the European American population of the Exome Sequencing Project. Cultured fibroblasts from an individual compound heterozygous for the p.Gly315Ser variant was found to have enzyme activity 20% of wild type but mRNA levels were found to be near normal (Maiti et al. 2009). Based on the evidence, the p.Gly315Ser variant is classified as pathogenic for SEPN1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
Likely pathogenic
(May 06, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Eichsfeld type congenital muscular dystrophy
Congenital myopathy 4A, autosomal dominant (Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
|
Undiagnosed Diseases Network, NIH
Study: Undiagnosed Diseases Network (NIH), UDN
Accession: SCV000930584.1 First in ClinVar: Aug 04, 2019 Last updated: Aug 04, 2019 |
Number of individuals with the variant: 1
Clinical Features:
Velopharyngeal insufficiency (present) , Upslanted palpebral fissure (present) , Ulnar deviation of the wrist (present) , Triangular-shaped open mouth (present) , Thoracic kyphosis (present) , … (more)
Velopharyngeal insufficiency (present) , Upslanted palpebral fissure (present) , Ulnar deviation of the wrist (present) , Triangular-shaped open mouth (present) , Thoracic kyphosis (present) , Short hard palate (present) , Scoliosis (present) , Restrictive deficit on pulmonary function testing (present) , Pulmonary embolism (present) , Obstructive sleep apnea syndrome (present) , Muscular Diseases (present) , Myopathic facies (present) , Limited pronation/supination of forearm (present) , Limited knee flexion/extension (present) , Hyporeflexia (present) , Hypoplasia of the radius (present) , Hyperlordosis (present) , Hyperemesis gravidarum (present) , Hip contracture (present) , High palate (present) , Gastroparesis (present) , EMG: myopathic abnormalities (present) , Broad thumb (present) (less)
Age: 30-39 years
Sex: female
Ethnicity/Population group: White
Testing laboratory: HudsonAlpha
Date variant was reported to submitter: 2018-08-02
Testing laboratory interpretation: Likely pathogenic
|
|
Pathogenic
(Dec 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital myopathy 4A, autosomal dominant
Affected status: yes
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV001520479.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
Pathogenic
(May 24, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital myopathy 4A, autosomal dominant
Affected status: yes
Allele origin:
germline
|
Centogene AG - the Rare Disease Company
Accession: SCV002059710.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
|
|
Likely pathogenic
(Dec 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501873.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 4
Secondary finding: no
|
|
Pathogenic
(Oct 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital myopathy 4A, autosomal dominant
Eichsfeld type congenital muscular dystrophy
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002807135.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(May 04, 2022)
|
criteria provided, single submitter
Method: curation
|
Eichsfeld type congenital muscular dystrophy
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV002507069.2
First in ClinVar: May 16, 2022 Last updated: Feb 07, 2023 |
Comment:
The heterozygous p.Gly315Ser variant in SELENON (also referred to as SEPN1) was identified by our study in the compound heterozygous state, along with an exonic … (more)
The heterozygous p.Gly315Ser variant in SELENON (also referred to as SEPN1) was identified by our study in the compound heterozygous state, along with an exonic deletion of uncertain significance, in one individual with SELENON-RM. This variant has been reported in at least 10 individuals with SELENON-RM (PMID: 16365872, 12192640, 17951086), segregated with disease in 5 affected relatives from 4 families (PMID: 12192640, 16365872), and has been identified in 0.037% (48/128676) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs121908188). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID#: 4496) and has been interpreted as pathogenic/likely pathogenic by multiple labs. Of the many affected individuals, 2 of those were homozygotes and 1 was a compound heterozygote that carried a reported pathogenic variant in trans, which increases the likelihood that the p.Gly315Ser variant is pathogenic (Variation ID: 4492,95958; PMID: 12192640, 17951086). In vitro functional studies provide some evidence that the variant may slightly impact protein function (PMID: 19067361). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive SELENON-RM. ACMG/AMP Criteria applied: PP1_strong, PM3_strong, PP3, PS3_supporting (Richards 2015). (less)
|
|
Likely pathogenic
(Mar 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital myopathy 4A, autosomal dominant
Eichsfeld type congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920893.1
First in ClinVar: May 06, 2023 Last updated: May 06, 2023 |
Comment:
SELENON NM_020451.2 exon 7 p.Gly315Ser (c.943G>A): (Gene also referred to as SEPN1) This variant has been reported in the literature in the homozygous or compound … (more)
SELENON NM_020451.2 exon 7 p.Gly315Ser (c.943G>A): (Gene also referred to as SEPN1) This variant has been reported in the literature in the homozygous or compound heterozygous state in several individuals with congenital myopathies, segregating with disease in at least 4 affected family members (Ferreiro 2002 PMID:12192640, Clarke 2006 PMID:16365872, Schara 2008 PMID:17951086, Maggi 2013 PMID:23394784). This variant is present in 0.03% (48/128676) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/1-26136244-G-A). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:4496). Evolutionary conservation and computational predictive tools support that this variant may impact the protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic. (less)
|
|
Pathogenic
(Sep 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000322094.9
First in ClinVar: Oct 09, 2016 Last updated: Sep 22, 2023 |
Comment:
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: 15668457, … (more)
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: 15668457, 20301436, 23394784, 12192640, 16365872, 15122708, 28688748, 31127727, 31321302, 30932294, 31561939, 33726816) (less)
|
|
Pathogenic
(Apr 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000809113.2
First in ClinVar: Sep 30, 2018 Last updated: Jan 26, 2024 |
Comment:
PP3, PM2, PM3_strong, PS3_supporting, PS4
Number of individuals with the variant: 1
|
|
Pathogenic
(Mar 01, 2006)
|
no assertion criteria provided
Method: literature only
|
CONGENITAL MYOPATHY 3 WITH RIGID SPINE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024929.5
First in ClinVar: Apr 04, 2013 Last updated: Apr 30, 2023 |
Comment on evidence:
In affected members of 2 unrelated families with congenital myopathy-3 with rigid spine (CMYP3; 602771) from Belgium and the U.K., Ferreiro et al. (2002) identified … (more)
In affected members of 2 unrelated families with congenital myopathy-3 with rigid spine (CMYP3; 602771) from Belgium and the U.K., Ferreiro et al. (2002) identified a homozygous c.943G-A transition in the SEPN1 gene, resulting in a gly315-to-ser (G315S) substitution. Haplotype analysis suggested a founder effect. A German patient with sporadic CMYP3 presented the same mutation in the compound heterozygous state with R466Q (606210.0004). Venance et al. (2005) identified a homozygous G315S mutation in a patient with CMYP3 who presented at age 26 years with cor pulmonale characterized by rapidly progressive respiratory and right heart failure with cough, orthopnea, and daytime sleepiness. Two sibs who were heterozygous carriers of the mutation had mild neck restriction. Venance et al. (2005) emphasized the importance of early nocturnal ventilatory assistance in these patients. In 5 patients from 2 unrelated families with CMYP3, Clarke et al. (2006) identified a homozygous G315S mutation. All 5 patients had abnormal glucose tolerance tests and showed biochemical abnormalities suggesting insulin resistance. Villar-Quiles et al. (2020) stated that G315S was a founder mutation in northern Europe. (less)
|
|
Pathogenic
(Mar 04, 2015)
|
no assertion criteria provided
Method: research
|
Muscular dystrophy, rigid spine, 1
Affected status: no
Allele origin:
germline
|
Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000238454.1 First in ClinVar: Jul 05, 2015 Last updated: Jul 05, 2015 |
Comment:
The SEPN1 variant (c. 943G>A) was identified in several patients in the literature and a disease-specific database (Ferreiro et al. 2002, PMID: 12192640; Venance et … (more)
The SEPN1 variant (c. 943G>A) was identified in several patients in the literature and a disease-specific database (Ferreiro et al. 2002, PMID: 12192640; Venance et al. 2005, PMID: 15668457; Clarke et al. 2006, PMID: 16365872; Schara et al. 2008, PMID: 17951086; Maggi et al. 2013, PMID: 23394784). Protein levels tested from fibroblast cells of an affected patient showed reduced activity of the protein (Maiti et al. 2009, PMID: 19067361). (less)
|
|
Pathogenic
(Mar 04, 2015)
|
no assertion criteria provided
Method: research
|
Myopathy, congenital, with fiber-type disproportion
Affected status: no
Allele origin:
germline
|
Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000238453.1 First in ClinVar: Jul 05, 2015 Last updated: Jul 05, 2015 |
Comment:
The SEPN1 variant (c. 943G>A) was identified in several patients in the literature and a disease-specific database (Ferreiro et al. 2002, PMID: 12192640; Venance et … (more)
The SEPN1 variant (c. 943G>A) was identified in several patients in the literature and a disease-specific database (Ferreiro et al. 2002, PMID: 12192640; Venance et al. 2005, PMID: 15668457; Clarke et al. 2006, PMID: 16365872; Schara et al. 2008, PMID: 17951086; Maggi et al. 2013, PMID: 23394784). Protein levels tested from fibroblast cells of an affected patient showed reduced activity of the protein (Maiti et al. 2009, PMID: 19067361). (less)
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Congenital myopathy with fiber type disproportion
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000058549.2
First in ClinVar: May 03, 2013 Last updated: Oct 01, 2022 |
|
|
click to load more click to collapse |
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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
The clinical, histologic, and genotypic spectrum of SEPN1-related myopathy: A case series. | Villar-Quiles RN | Neurology | 2020 | PMID: 32796131 |
Congenital myopathies in the adult neuromuscular clinic: Diagnostic challenges and pitfalls. | Nicolau S | Neurology. Genetics | 2019 | PMID: 31321302 |
Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service. | Westra D | Journal of neuromuscular diseases | 2019 | PMID: 31127727 |
Aberrant regulation of epigenetic modifiers contributes to the pathogenesis in patients with selenoprotein N-related myopathies. | Bachmann C | Human mutation | 2019 | PMID: 30932294 |
Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. | Maggi L | Neuromuscular disorders : NMD | 2013 | PMID: 23394784 |
Congenital Fiber-Type Disproportion – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. | Adam MP | - | 2013 | PMID: 20301436 |
The phenotype and long-term follow-up in 11 patients with juvenile selenoprotein N1-related myopathy. | Schara U | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | 2008 | PMID: 17951086 |
Abnormal distribution of calcium-handling proteins: a novel distinctive marker in core myopathies. | Herasse M | Journal of neuropathology and experimental neurology | 2007 | PMID: 17204937 |
SEPN1: associated with congenital fiber-type disproportion and insulin resistance. | Clarke NF | Annals of neurology | 2006 | PMID: 16365872 |
Rigid spine muscular dystrophy due to SEPN1 mutation presenting as cor pulmonale. | Venance SL | Neurology | 2005 | PMID: 15668457 |
Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene. | Ferreiro A | Annals of neurology | 2004 | PMID: 15122708 |
Mutations of the selenoprotein N gene, which is implicated in rigid spine muscular dystrophy, cause the classical phenotype of multiminicore disease: reassessing the nosology of early-onset myopathies. | Ferreiro A | American journal of human genetics | 2002 | PMID: 12192640 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SELENON | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs121908188 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.