rs770836890
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000083.3(CLCN1):c.2062_2063insTTC(p.Gly688delinsValArg) variant causes a protein altering change. The variant allele was found at a frequency of 0.000053 in 1,565,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
CLCN1
NM_000083.3 protein_altering
NM_000083.3 protein_altering
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
CLCN1 (HGNC:2019): (chloride voltage-gated channel 1) The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. The protein encoded by this gene regulates the electric excitability of the skeletal muscle membrane. Mutations in this gene cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.2062_2063insTTC | p.Gly688delinsValArg | protein_altering_variant | 17/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.2017_2018insTTC | non_coding_transcript_exon_variant | 16/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.2062_2063insTTC | p.Gly688delinsValArg | protein_altering_variant | 17/23 | 1 | NM_000083.3 | P4 | |
CLCN1 | ENST00000432192.6 | c.*1347_*1348insTTC | 3_prime_UTR_variant, NMD_transcript_variant | 17/23 | 1 | ||||
CLCN1 | ENST00000650516.2 | c.2062_2063insTTC | p.Gly688delinsValArg | protein_altering_variant | 17/23 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
12
AN:
152206
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000146 AC: 25AN: 170760Hom.: 0 AF XY: 0.000131 AC XY: 12AN XY: 91840
GnomAD3 exomes
AF:
AC:
25
AN:
170760
Hom.:
AF XY:
AC XY:
12
AN XY:
91840
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000502 AC: 71AN: 1413386Hom.: 0 Cov.: 33 AF XY: 0.0000458 AC XY: 32AN XY: 698704
GnomAD4 exome
AF:
AC:
71
AN:
1413386
Hom.:
Cov.:
33
AF XY:
AC XY:
32
AN XY:
698704
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74354
GnomAD4 genome
?
AF:
AC:
12
AN:
152206
Hom.:
Cov.:
32
AF XY:
AC XY:
7
AN XY:
74354
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 22, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 20, 2016 | The c.2062_2063insTTC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in the Exome Aggregation Consortium (ExAC) data set, indicating it is not a benign variant in these populations. The c.2062_2063insTTC variant results in the replacement of a Glycine residue with a Valine residue, and the insertion of a single Arginine residue, denoted p.Gly688delinsValR. In-silico analysis predicts this variant does not affect gene splicing. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 27, 2017 | - - |
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at