NM_001927.4:c.1012C>T

Variant names:

• chr2-219420942-C-T
• NM_001927.4:c.1012C>T
• DES p.Leu338Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001927.4(DES):​c.1012C>T​(p.Leu338Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L338L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DES NM_001927.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

DES (HGNC:2770): (desmin) This gene encodes a muscle-specific class III intermediate filament. Homopolymers of this protein form a stable intracytoplasmic filamentous network connecting myofibrils to each other and to the plasma membrane. Mutations in this gene are associated with desmin-related myopathy, a familial cardiac and skeletal myopathy (CSM), and with distal myopathies. [provided by RefSeq, Jul 2008]

DES Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1I

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• myofibrillar myopathy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• myofibrillar myopathy 1

  Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• atrioventricular block

  Inheritance: AR, AD Classification: STRONG Submitted by: Genomics England PanelApp
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neurogenic scapuloperoneal syndrome, Kaeser type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001927.4. 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
	DES	NM_001927.4	MANE Select	c.1012C>T	p.Leu338Leu	synonymous	Exon 5 of 9	NP_001918.3
	DES	NM_001382708.1		c.1009C>T	p.Leu337Leu	synonymous	Exon 5 of 9	NP_001369637.1
	DES	NM_001382712.1		c.1012C>T	p.Leu338Leu	synonymous	Exon 5 of 9	NP_001369641.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DES	ENST00000373960.4	TSL:1 MANE Select	c.1012C>T	p.Leu338Leu	synonymous	Exon 5 of 9	ENSP00000363071.3	P17661
	DES	ENST00000942906.1		c.1012C>T	p.Leu338Leu	synonymous	Exon 5 of 10	ENSP00000612965.1
	DES	ENST00000942898.1		c.1012C>T	p.Leu338Leu	synonymous	Exon 5 of 9	ENSP00000612957.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		6.0
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr2-220285664;