CALM1 p.Arg91Arg

Variant names:

• chr14-90403953-C-C
• NM_006888.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr14-90403954--
• chr14-90403956-A-T
• chr14-90403956-A-C
• chr14-90403956-A-G
• chr14-90403954-C-A
• chr14-90403954-CGA-AGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006888.6(CALM1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALM1 NM_006888.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

Genes affected

CALM1 (HGNC:1442): (calmodulin 1) This gene encodes one of three calmodulin proteins which are members of the EF-hand calcium-binding protein family. Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. Two pseudogenes have been identified on chromosome 7 and X. Multiple transcript variants encoding different isoforms have been found for this gene.A missense mutation in the CALM1 gene has been associated with ventricular tachycardia.[provided by RefSeq, May 2020]

CALM1 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• long QT syndrome 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
• catecholaminergic polymorphic ventricular tachycardia 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ENSG00000258424 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006888.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	NM_006888.6	MANE Select	c.		exon_region	Exon 6 of 6	NP_008819.1	P0DP23
	CALM1	NM_006888.6	MANE Select	c.		3_prime_UTR	Exon 6 of 6	NP_008819.1	P0DP23
	CALM1	NM_001363670.2		c.		exon_region	Exon 6 of 6	NP_001350599.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	ENST00000356978.9	TSL:1 MANE Select	c.		intron	N/A	ENSP00000349467.4	P0DP23
	CALM1	ENST00000544280.6	TSL:1	c.		intron	N/A	ENSP00000442853.2	Q96HY3
	CALM1	ENST00000553964.5	TSL:1	n.		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-90870297;