NM_000069.3(CACNA1S):c.4569C>G (p.Phe1523Leu) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 4, 2019
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:: RCV001047961.7

Allele description

NM_000069.3(CACNA1S):c.4569C>G (p.Phe1523Leu)

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.4569C>G (p.Phe1523Leu)

HGVS:

NC_000001.11:g.201047214G>C
NG_009816.2:g.70353C>G
NM_000069.3:c.4569C>GMANE SELECT
NP_000060.2:p.Phe1523Leu
NC_000001.10:g.201016342G>C
NG_009816.1:g.70353C>G
NM_000069.2:c.4569C>G

Protein change:

F1523L

Links:

dbSNP: rs995172326

NCBI 1000 Genomes Browser:

rs995172326

Molecular consequence:

NM_000069.3:c.4569C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypokalemic periodic paralysis, type 1
Synonyms:: HypoPP
Identifiers:: MONDO: MONDO:0042979; MedGen: C3714580; Orphanet: 681; OMIM: 170400

Name:: Malignant hyperthermia, susceptibility to, 5 (MHS5)
Synonyms:: Malignant hyperthermia susceptibility type 5; Malignant hyperpyrexia susceptibility type 5
Identifiers:: MONDO: MONDO:0011163; MedGen: C1866077; Orphanet: 423; OMIM: 601887

Recent activity

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adhesion G-protein coupled receptor G1 isoform X3 [Homo sapiens]
adhesion G-protein coupled receptor G1 isoform X3 [Homo sapiens]
gi|2462551747|ref|XP_054170377.1|

Protein
Homo sapiens adhesion G protein-coupled receptor G1 (ADGRG1), transcript variant...
Homo sapiens adhesion G protein-coupled receptor G1 (ADGRG1), transcript variant 26, mRNA
gi|1635381391|ref|NM_001370442.1|

Nucleotide
PREDICTED: Homo sapiens adhesion G protein-coupled receptor G1 (ADGRG1), transcr...
PREDICTED: Homo sapiens adhesion G protein-coupled receptor G1 (ADGRG1), transcript variant X33, mRNA
gi|2217308242|ref|XM_047434916.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211947	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 4, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211947

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 4, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001211947.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CACNA1S-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 1523 of the CACNA1S protein (p.Phe1523Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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