NM_000069.3(CACNA1S):c.574_575del (p.Ala192fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 2, 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:: RCV003793662.1

Allele description [Variation Report for NM_000069.3(CACNA1S):c.574_575del (p.Ala192fs)]

NM_000069.3(CACNA1S):c.574_575del (p.Ala192fs)

Gene:

CACNA1S:calcium voltage-gated channel subunit alpha1 S [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q32.1

Genomic location:

Preferred name:

NM_000069.3(CACNA1S):c.574_575del (p.Ala192fs)

HGVS:

NC_000001.11:g.201091759_201091760del
NG_009816.2:g.25807_25808del
NM_000069.3:c.574_575delMANE SELECT
NP_000060.2:p.Ala192fs
NC_000001.10:g.201060887_201060888del

Protein change:

A192fs

Molecular consequence:

NM_000069.3:c.574_575del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004581638	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26247046, 28012042, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004581638

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 2, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Novel pathogenic variants and genes for myopathies identified by whole exome sequencing.

Hunter JM, Ahearn ME, Balak CD, Liang WS, Kurdoglu A, Corneveaux JJ, Russell M, Huentelman MJ, Craig DW, Carpten J, Coons SW, DeMello DE, Hall JG, Bernes SM, Baumbach-Reardon L.

Mol Genet Genomic Med. 2015 Jul;3(4):283-301. doi: 10.1002/mgg3.142. Epub 2015 Apr 8.

PubMed [citation]

PMID:: 26247046
PMCID:: PMC4521965

Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy.

Schartner V, Romero NB, Donkervoort S, Treves S, Munot P, Pierson TM, Dabaj I, Malfatti E, Zaharieva IT, Zorzato F, Abath Neto O, Brochier G, Lornage X, Eymard B, Taratuto AL, Böhm J, Gonorazky H, Ramos-Platt L, Feng L, Phadke R, Bharucha-Goebel DX, Sumner CJ, et al.

Acta Neuropathol. 2017 Apr;133(4):517-533. doi: 10.1007/s00401-016-1656-8. Epub 2016 Dec 23.

PubMed [citation]

PMID:: 28012042

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004581638.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is present in population databases (no rsID available, gnomAD 0.006%). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. This sequence change creates a premature translational stop signal (p.Ala192Hisfs*48) in the CACNA1S gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1S are known to be pathogenic (PMID: 26247046, 28012042).

#	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: Mar 5, 2024

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