TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20402	61429;61430;61431	chr2:178590521;178590520;178590519	chr2:179455248;179455247;179455246
N2AB	18761	56506;56507;56508	chr2:178590521;178590520;178590519	chr2:179455248;179455247;179455246
N2A	17834	53725;53726;53727	chr2:178590521;178590520;178590519	chr2:179455248;179455247;179455246
N2B	11337	34234;34235;34236	chr2:178590521;178590520;178590519	chr2:179455248;179455247;179455246
Novex-1	11462	34609;34610;34611	chr2:178590521;178590520;178590519	chr2:179455248;179455247;179455246
Novex-2	11529	34810;34811;34812	chr2:178590521;178590520;178590519	chr2:179455248;179455247;179455246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-36
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6041
• 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
P/H	None	None	1.0	N	0.628	0.464	0.432826170204	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
P/A	0.1808	likely_benign	0.1574	benign	-0.584	Destabilizing	0.767	D	0.435	neutral	N	0.497769882	None	None	I
P/C	0.8401	likely_pathogenic	0.7894	pathogenic	-0.684	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
P/D	0.7589	likely_pathogenic	0.7015	pathogenic	-0.185	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
P/E	0.5547	ambiguous	0.4753	ambiguous	-0.277	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
P/F	0.8916	likely_pathogenic	0.8536	pathogenic	-0.655	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
P/G	0.6977	likely_pathogenic	0.6295	pathogenic	-0.754	Destabilizing	0.997	D	0.608	neutral	None	None	None	None	I
P/H	0.5231	ambiguous	0.4453	ambiguous	-0.242	Destabilizing	1.0	D	0.628	neutral	N	0.481726542	None	None	I
P/I	0.6516	likely_pathogenic	0.5918	pathogenic	-0.277	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
P/K	0.621	likely_pathogenic	0.5074	ambiguous	-0.493	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/L	0.3545	ambiguous	0.3091	benign	-0.277	Destabilizing	0.999	D	0.669	neutral	N	0.487411308	None	None	I
P/M	0.636	likely_pathogenic	0.5778	pathogenic	-0.346	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	I
P/N	0.6686	likely_pathogenic	0.5779	pathogenic	-0.248	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
P/Q	0.3807	ambiguous	0.3121	benign	-0.464	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
P/R	0.4801	ambiguous	0.3941	ambiguous	0.021	Stabilizing	0.999	D	0.669	neutral	N	0.465304127	None	None	I
P/S	0.364	ambiguous	0.287	benign	-0.682	Destabilizing	0.998	D	0.614	neutral	N	0.470001388	None	None	I
P/T	0.3122	likely_benign	0.2482	benign	-0.664	Destabilizing	0.999	D	0.616	neutral	N	0.473141714	None	None	I
P/V	0.4441	ambiguous	0.3984	ambiguous	-0.343	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
P/W	0.9466	likely_pathogenic	0.9242	pathogenic	-0.731	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
P/Y	0.8477	likely_pathogenic	0.7899	pathogenic	-0.44	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.