NM_006888.6(CALM1):c.293A>G (p.Asn98Ser) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 3, 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:: RCV000526484.14

Allele description [Variation Report for NM_006888.6(CALM1):c.293A>G (p.Asn98Ser)]

NM_006888.6(CALM1):c.293A>G (p.Asn98Ser)

Gene:

CALM1:calmodulin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.11

Genomic location:

Preferred name:

NM_006888.6(CALM1):c.293A>G (p.Asn98Ser)

Other names:

N97S

HGVS:

NC_000014.9:g.90404386A>G
NG_013338.1:g.12404A>G
NM_001363669.2:c.185A>G
NM_001363670.2:c.296A>G
NM_006888.6:c.293A>GMANE SELECT
NP_001350598.1:p.Asn62Ser
NP_001350599.1:p.Asn99Ser
NP_008819.1:p.Asn98Ser
NC_000014.8:g.90870730A>G
NM_006888.4:c.293A>G
NM_006888.5:c.293A>G
NP_008819.1:p.Asn98Ser(Asn97Ser)
P62158:p.Asn98Ser

Note:

NCBI staff reviewed the sequence information reported in PubMed 23040497 to determine the location of this allele on the current reference sequence. Their numbering of Asn97Ser, when begun at Met1, will be Asn98Ser.

Protein change:

N62S; ASN97SER

Links:

UniProtKB: P62158#VAR_069223; OMIM: 114180.0002; dbSNP: rs267607277

NCBI 1000 Genomes Browser:

rs267607277

Molecular consequence:

NM_001363669.2:c.185A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363670.2:c.296A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006888.6:c.293A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Catecholaminergic polymorphic ventricular tachycardia 4
Identifiers:: MONDO: MONDO:0013966; MedGen: C3554047; Orphanet: 3286; OMIM: 614916

Name:: Long QT syndrome 14 (LQT14)
Identifiers:: MONDO: MONDO:0014548; MedGen: C4015671; Orphanet: 101016; Orphanet: 768; OMIM: 616247

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000655574	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 3, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 23040497, 24563457, 24816216, 25557436, 26309258, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000655574

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 3, 2023)

germline

clinical testing

PubMed (6)
[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

Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.

Nyegaard M, Overgaard MT, Søndergaard MT, Vranas M, Behr ER, Hildebrandt LL, Lund J, Hedley PL, Camm AJ, Wettrell G, Fosdal I, Christiansen M, Børglum AD.

Am J Hum Genet. 2012 Oct 5;91(4):703-12. doi: 10.1016/j.ajhg.2012.08.015.

PubMed [citation]

PMID:: 23040497
PMCID:: PMC3484646

Divergent regulation of ryanodine receptor 2 calcium release channels by arrhythmogenic human calmodulin missense mutants.

Hwang HS, Nitu FR, Yang Y, Walweel K, Pereira L, Johnson CN, Faggioni M, Chazin WJ, Laver D, George AL Jr, Cornea RL, Bers DM, Knollmann BC.

Circ Res. 2014 Mar 28;114(7):1114-24. doi: 10.1161/CIRCRESAHA.114.303391. Epub 2014 Feb 21.

PubMed [citation]

PMID:: 24563457
PMCID:: PMC3990285

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000655574.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This missense change has been observed in individual(s) with catecholaminergic polymorphic VT (PMID: 23040497). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 98 of the CALM1 protein (p.Asn98Ser). This variant is also known as p.Asn97Ser. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CALM1 function (PMID: 23040497, 24563457, 24816216, 25557436, 26309258). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 39758).

#	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: Jun 9, 2024

ClinVar

Relating variation to medicine