TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32652	98179;98180;98181	chr2:178540212;178540211;178540210	chr2:179404939;179404938;179404937
N2AB	31011	93256;93257;93258	chr2:178540212;178540211;178540210	chr2:179404939;179404938;179404937
N2A	30084	90475;90476;90477	chr2:178540212;178540211;178540210	chr2:179404939;179404938;179404937
N2B	23587	70984;70985;70986	chr2:178540212;178540211;178540210	chr2:179404939;179404938;179404937
Novex-1	23712	71359;71360;71361	chr2:178540212;178540211;178540210	chr2:179404939;179404938;179404937
Novex-2	23779	71560;71561;71562	chr2:178540212;178540211;178540210	chr2:179404939;179404938;179404937
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-126
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6893
• 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
T/S	None	None	0.999	N	0.527	0.313	0.266385636622	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1344	likely_benign	0.1501	benign	-0.126	Destabilizing	0.999	D	0.513	neutral	N	0.499354323	None	None	I
T/C	0.6335	likely_pathogenic	0.6478	pathogenic	-0.283	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	I
T/D	0.6145	likely_pathogenic	0.6283	pathogenic	0.109	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	I
T/E	0.5171	ambiguous	0.5346	ambiguous	0.022	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	I
T/F	0.5095	ambiguous	0.5139	ambiguous	-0.769	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
T/G	0.4155	ambiguous	0.4391	ambiguous	-0.201	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	I
T/H	0.449	ambiguous	0.4548	ambiguous	-0.39	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	I
T/I	0.3396	likely_benign	0.367	ambiguous	-0.054	Destabilizing	1.0	D	0.631	neutral	N	0.471454009	None	None	I
T/K	0.4112	ambiguous	0.4239	ambiguous	-0.229	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
T/L	0.1824	likely_benign	0.1933	benign	-0.054	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	I
T/M	0.1464	likely_benign	0.1631	benign	-0.103	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
T/N	0.2513	likely_benign	0.2573	benign	-0.01	Destabilizing	1.0	D	0.669	neutral	N	0.518980234	None	None	I
T/P	0.2516	likely_benign	0.2652	benign	-0.053	Destabilizing	1.0	D	0.619	neutral	N	0.500357188	None	None	I
T/Q	0.3739	ambiguous	0.3819	ambiguous	-0.207	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
T/R	0.3604	ambiguous	0.3861	ambiguous	0.038	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	I
T/S	0.2037	likely_benign	0.2158	benign	-0.175	Destabilizing	0.999	D	0.527	neutral	N	0.508552597	None	None	I
T/V	0.2284	likely_benign	0.246	benign	-0.053	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	I
T/W	0.7967	likely_pathogenic	0.8138	pathogenic	-0.862	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
T/Y	0.4807	ambiguous	0.4989	ambiguous	-0.531	Destabilizing	1.0	D	0.639	neutral	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.