TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23493	70702;70703;70704	chr2:178575655;178575654;178575653	chr2:179440382;179440381;179440380
N2AB	21852	65779;65780;65781	chr2:178575655;178575654;178575653	chr2:179440382;179440381;179440380
N2A	20925	62998;62999;63000	chr2:178575655;178575654;178575653	chr2:179440382;179440381;179440380
N2B	14428	43507;43508;43509	chr2:178575655;178575654;178575653	chr2:179440382;179440381;179440380
Novex-1	14553	43882;43883;43884	chr2:178575655;178575654;178575653	chr2:179440382;179440381;179440380
Novex-2	14620	44083;44084;44085	chr2:178575655;178575654;178575653	chr2:179440382;179440381;179440380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-58
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.2176
• 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
T/I	None	None	0.815	N	0.516	0.336	0.385906861911	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	0	0
T/S	rs375675901	None	0.004	N	0.188	0.093	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
T/S	rs375675901	None	0.004	N	0.188	0.093	None	gnomAD-4.0.0	7.43708E-06	None	None	None	None	N	None	6.67485E-05	0	None	0	0	None	0	0	5.08613E-06	0	1.60128E-05

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	0.0914	likely_benign	0.091	benign	-0.906	Destabilizing	0.164	N	0.296	neutral	N	0.507515234	None	None	N
T/C	0.3604	ambiguous	0.3811	ambiguous	-0.415	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	N
T/D	0.5258	ambiguous	0.5829	pathogenic	-0.897	Destabilizing	0.742	D	0.438	neutral	None	None	None	None	N
T/E	0.5183	ambiguous	0.5509	ambiguous	-0.788	Destabilizing	0.543	D	0.434	neutral	None	None	None	None	N
T/F	0.2082	likely_benign	0.245	benign	-0.573	Destabilizing	0.984	D	0.565	neutral	None	None	None	None	N
T/G	0.2238	likely_benign	0.2392	benign	-1.266	Destabilizing	0.373	N	0.445	neutral	None	None	None	None	N
T/H	0.2607	likely_benign	0.2837	benign	-1.483	Destabilizing	0.953	D	0.57	neutral	None	None	None	None	N
T/I	0.18	likely_benign	0.1871	benign	0.01	Stabilizing	0.815	D	0.516	neutral	N	0.473841228	None	None	N
T/K	0.4287	ambiguous	0.4616	ambiguous	-0.916	Destabilizing	0.309	N	0.418	neutral	N	0.479675271	None	None	N
T/L	0.1086	likely_benign	0.1108	benign	0.01	Stabilizing	0.543	D	0.435	neutral	None	None	None	None	N
T/M	0.101	likely_benign	0.1076	benign	0.144	Stabilizing	0.984	D	0.518	neutral	None	None	None	None	N
T/N	0.1219	likely_benign	0.1389	benign	-1.137	Destabilizing	0.742	D	0.417	neutral	None	None	None	None	N
T/P	0.5651	likely_pathogenic	0.5473	ambiguous	-0.264	Destabilizing	0.815	D	0.485	neutral	N	0.518348303	None	None	N
T/Q	0.3116	likely_benign	0.3223	benign	-1.02	Destabilizing	0.742	D	0.477	neutral	None	None	None	None	N
T/R	0.3455	ambiguous	0.3634	ambiguous	-0.917	Destabilizing	0.007	N	0.269	neutral	N	0.476480251	None	None	N
T/S	0.0744	likely_benign	0.0812	benign	-1.33	Destabilizing	0.004	N	0.188	neutral	N	0.36711777	None	None	N
T/V	0.1482	likely_benign	0.1507	benign	-0.264	Destabilizing	0.742	D	0.404	neutral	None	None	None	None	N
T/W	0.6142	likely_pathogenic	0.6582	pathogenic	-0.732	Destabilizing	0.996	D	0.588	neutral	None	None	None	None	N
T/Y	0.2728	likely_benign	0.3108	benign	-0.452	Destabilizing	0.984	D	0.557	neutral	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.