TBX20 p.Gly435Arg

Variant names:

• chr7-35202471-C-G
• NM_001077653.2:c.1303G>C
• TBX20 p.Gly435Arg

Your query was ambiguous. Multiple possible variants found:

• chr7-35202471-C-G
• chr7-35202471-C-T
• chr7-35202469-TCC-ACG
• chr7-35202469-TCC-GCG
• chr7-35202469-TCC-CCG
• chr7-35202469-TCC-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001077653.2(TBX20):​c.1303G>C​(p.Gly435Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TBX20 NM_001077653.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

TBX20 (HGNC:11598): (T-box transcription factor 20) This gene encodes a T-box family member. The T-box family members share a common DNA binding domain, termed the T-box, and they are transcription factors involved in the regulation of developmental processes. This gene is essential for heart development. Mutations in this gene are associated with diverse cardiac pathologies, including defects in septation, valvulogenesis and cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

TBX20 Gene-Disease associations (from GenCC):

• atrial septal defect 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• dilated cardiomyopathy

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000294801 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077653.2. 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
	TBX20	NM_001077653.2	MANE Select	c.1303G>C	p.Gly435Arg	missense	Exon 8 of 8	NP_001071121.1	Q9UMR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX20	ENST00000408931.4	TSL:1 MANE Select	c.1303G>C	p.Gly435Arg	missense	Exon 8 of 8	ENSP00000386170.3	Q9UMR3
	ENSG00000294801	ENST00000726058.1		n.453C>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000294801	ENST00000726056.1		n.166+455C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.55	N
PhyloP100		7.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.010	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.096	T
Varity_R		0.17
gMVP		0.59
Mutation Taster		=9/91	disease causing

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: chr7-35242083;