TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9211	27856;27857;27858	chr2:178712199;178712198;178712197	chr2:179576926;179576925;179576924
N2AB	8894	26905;26906;26907	chr2:178712199;178712198;178712197	chr2:179576926;179576925;179576924
N2A	7967	24124;24125;24126	chr2:178712199;178712198;178712197	chr2:179576926;179576925;179576924
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-78
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2197
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
L/F	rs1197586368	None	0.864	N	0.622	0.283	0.346315397577	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
L/A	0.5471	ambiguous	0.5581	ambiguous	-2.174	Highly Destabilizing	0.547	D	0.535	neutral	None	None	None	None	I
L/C	0.8407	likely_pathogenic	0.8501	pathogenic	-1.433	Destabilizing	0.995	D	0.71	prob.delet.	None	None	None	None	I
L/D	0.9792	likely_pathogenic	0.9802	pathogenic	-1.954	Destabilizing	0.945	D	0.811	deleterious	None	None	None	None	I
L/E	0.8977	likely_pathogenic	0.8948	pathogenic	-1.801	Destabilizing	0.945	D	0.795	deleterious	None	None	None	None	I
L/F	0.4233	ambiguous	0.4796	ambiguous	-1.274	Destabilizing	0.864	D	0.622	neutral	N	0.497793335	None	None	I
L/G	0.8718	likely_pathogenic	0.8751	pathogenic	-2.662	Highly Destabilizing	0.945	D	0.785	deleterious	None	None	None	None	I
L/H	0.8643	likely_pathogenic	0.8762	pathogenic	-2.035	Highly Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	I
L/I	0.1549	likely_benign	0.1498	benign	-0.809	Destabilizing	0.547	D	0.504	neutral	None	None	None	None	I
L/K	0.8771	likely_pathogenic	0.8787	pathogenic	-1.442	Destabilizing	0.894	D	0.721	prob.delet.	None	None	None	None	I
L/M	0.1357	likely_benign	0.1471	benign	-0.751	Destabilizing	0.053	N	0.351	neutral	N	0.473359204	None	None	I
L/N	0.9119	likely_pathogenic	0.9151	pathogenic	-1.526	Destabilizing	0.945	D	0.816	deleterious	None	None	None	None	I
L/P	0.321	likely_benign	0.342	ambiguous	-1.239	Destabilizing	0.017	N	0.485	neutral	None	None	None	None	I
L/Q	0.7079	likely_pathogenic	0.7161	pathogenic	-1.5	Destabilizing	0.894	D	0.775	deleterious	None	None	None	None	I
L/R	0.8249	likely_pathogenic	0.8303	pathogenic	-1.118	Destabilizing	0.894	D	0.774	deleterious	None	None	None	None	I
L/S	0.8268	likely_pathogenic	0.8354	pathogenic	-2.266	Highly Destabilizing	0.864	D	0.709	prob.delet.	N	0.470067522	None	None	I
L/T	0.5501	ambiguous	0.5697	pathogenic	-1.975	Destabilizing	0.894	D	0.7	prob.neutral	None	None	None	None	I
L/V	0.1663	likely_benign	0.1629	benign	-1.239	Destabilizing	0.477	N	0.461	neutral	N	0.479182101	None	None	I
L/W	0.7312	likely_pathogenic	0.7607	pathogenic	-1.549	Destabilizing	0.993	D	0.753	deleterious	N	0.503833723	None	None	I
L/Y	0.8885	likely_pathogenic	0.9033	pathogenic	-1.267	Destabilizing	0.945	D	0.752	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.