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NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu) AND CACNA1S-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 13, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003419987.4

Allele description [Variation Report for NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu)]

NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu)

Gene:
CACNA1S:calcium voltage-gated channel subunit alpha1 S [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_000069.3(CACNA1S):c.1583G>T (p.Arg528Leu)
HGVS:
  • NC_000001.11:g.201077915C>A
  • NG_009816.2:g.39652G>T
  • NM_000069.3:c.1583G>TMANE SELECT
  • NP_000060.2:p.Arg528Leu
  • NC_000001.10:g.201047043C>A
  • NG_009816.1:g.39652G>T
  • NM_000069.2:c.1583G>T
Protein change:
R528L
Links:
dbSNP: rs80338777
NCBI 1000 Genomes Browser:
rs80338777
Molecular consequence:
  • NM_000069.3:c.1583G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
CACNA1S-related disorder
Synonyms:
CACNA1S-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004114546PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Apr 13, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004114546.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The CACNA1S c.1583G>T variant is predicted to result in the amino acid substitution p.Arg528Leu. This variant has been reported in at least six families with CACNA1S-related disease (Anandan et al. 2018. PubMed ID: 29193480; Table e-1 - Nicolau et al. 2019. PubMed ID: 31321302). Additionally, multiple missense variants impacting this amino acid (p.Arg528His, p.Arg528Cys, p.Arg528Gly) have been reported as pathogenic (Katsuno et al. 2001. PubMed ID: 11808349; Yang et al. 2014. PubMed ID: 25430699; Wang et al. 2005. PubMed ID: 15726306). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-201047043-C-A) and has been interpreted as likely pathogenic by multiple labs in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/473965/). This variant is interpreted as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024