TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35437	106534;106535;106536	chr2:178530306;178530305;178530304	chr2:179395033;179395032;179395031
N2AB	33796	101611;101612;101613	chr2:178530306;178530305;178530304	chr2:179395033;179395032;179395031
N2A	32869	98830;98831;98832	chr2:178530306;178530305;178530304	chr2:179395033;179395032;179395031
N2B	26372	79339;79340;79341	chr2:178530306;178530305;178530304	chr2:179395033;179395032;179395031
Novex-1	26497	79714;79715;79716	chr2:178530306;178530305;178530304	chr2:179395033;179395032;179395031
Novex-2	26564	79915;79916;79917	chr2:178530306;178530305;178530304	chr2:179395033;179395032;179395031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-166
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1191
• Predicted PPI site: N

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
A/T	None	None	None	N	0.467	0.059	0.0846915920261	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
A/C	0.652	likely_pathogenic	0.6993	pathogenic	-0.885	Destabilizing	0.646	D	0.682	prob.neutral	None	None	None	None	N
A/D	0.858	likely_pathogenic	0.8882	pathogenic	-1.671	Destabilizing	0.153	N	0.772	deleterious	N	0.470370237	None	None	N
A/E	0.7199	likely_pathogenic	0.7492	pathogenic	-1.525	Destabilizing	0.193	N	0.787	deleterious	None	None	None	None	N
A/F	0.5891	likely_pathogenic	0.6648	pathogenic	-0.704	Destabilizing	0.193	N	0.787	deleterious	None	None	None	None	N
A/G	0.2542	likely_benign	0.2792	benign	-1.427	Destabilizing	0.049	N	0.677	prob.neutral	N	0.504042493	None	None	N
A/H	0.8841	likely_pathogenic	0.9101	pathogenic	-1.69	Destabilizing	0.848	D	0.733	prob.delet.	None	None	None	None	N
A/I	0.2785	likely_benign	0.3203	benign	0.14	Stabilizing	None	N	0.511	neutral	None	None	None	None	N
A/K	0.8518	likely_pathogenic	0.8751	pathogenic	-1.285	Destabilizing	0.193	N	0.793	deleterious	None	None	None	None	N
A/L	0.2595	likely_benign	0.3128	benign	0.14	Stabilizing	0.014	N	0.593	neutral	None	None	None	None	N
A/M	0.3604	ambiguous	0.4366	ambiguous	0.055	Stabilizing	0.193	N	0.755	deleterious	None	None	None	None	N
A/N	0.7625	likely_pathogenic	0.8131	pathogenic	-1.371	Destabilizing	0.193	N	0.785	deleterious	None	None	None	None	N
A/P	0.869	likely_pathogenic	0.8905	pathogenic	-0.191	Destabilizing	0.268	N	0.796	deleterious	N	0.463368797	None	None	N
A/Q	0.7157	likely_pathogenic	0.7506	pathogenic	-1.262	Destabilizing	0.326	N	0.765	deleterious	None	None	None	None	N
A/R	0.7924	likely_pathogenic	0.8171	pathogenic	-1.224	Destabilizing	0.193	N	0.798	deleterious	None	None	None	None	N
A/S	0.1781	likely_benign	0.2085	benign	-1.826	Destabilizing	0.025	N	0.631	neutral	N	0.5118539	None	None	N
A/T	0.1261	likely_benign	0.146	benign	-1.548	Destabilizing	None	N	0.467	neutral	N	0.462483872	None	None	N
A/V	0.1244	likely_benign	0.1407	benign	-0.191	Destabilizing	None	N	0.268	neutral	N	0.360601937	None	None	N
A/W	0.9263	likely_pathogenic	0.9502	pathogenic	-1.348	Destabilizing	0.848	D	0.769	deleterious	None	None	None	None	N
A/Y	0.8249	likely_pathogenic	0.8676	pathogenic	-0.788	Destabilizing	0.326	N	0.767	deleterious	None	None	None	None	N

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.