TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22096	66511;66512;66513	chr2:178582083;178582082;178582081	chr2:179446810;179446809;179446808
N2AB	20455	61588;61589;61590	chr2:178582083;178582082;178582081	chr2:179446810;179446809;179446808
N2A	19528	58807;58808;58809	chr2:178582083;178582082;178582081	chr2:179446810;179446809;179446808
N2B	13031	39316;39317;39318	chr2:178582083;178582082;178582081	chr2:179446810;179446809;179446808
Novex-1	13156	39691;39692;39693	chr2:178582083;178582082;178582081	chr2:179446810;179446809;179446808
Novex-2	13223	39892;39893;39894	chr2:178582083;178582082;178582081	chr2:179446810;179446809;179446808
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-48
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.5018
• 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
E/K	None	None	0.977	N	0.544	0.306	0.356281029322	gnomAD-4.0.0	1.5925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-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
E/A	0.5038	ambiguous	0.4849	ambiguous	-0.886	Destabilizing	0.977	D	0.619	neutral	N	0.478992561	None	None	N
E/C	0.9692	likely_pathogenic	0.973	pathogenic	-0.494	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/D	0.2515	likely_benign	0.3134	benign	-1.111	Destabilizing	0.117	N	0.21	neutral	N	0.486505243	None	None	N
E/F	0.9771	likely_pathogenic	0.9804	pathogenic	-0.384	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/G	0.6039	likely_pathogenic	0.5617	ambiguous	-1.246	Destabilizing	0.993	D	0.644	neutral	N	0.48757739	None	None	N
E/H	0.9014	likely_pathogenic	0.9009	pathogenic	-0.719	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/I	0.8245	likely_pathogenic	0.8359	pathogenic	0.097	Stabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
E/K	0.6928	likely_pathogenic	0.6368	pathogenic	-0.749	Destabilizing	0.977	D	0.544	neutral	N	0.509168672	None	None	N
E/L	0.8395	likely_pathogenic	0.8456	pathogenic	0.097	Stabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
E/M	0.8569	likely_pathogenic	0.8563	pathogenic	0.544	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/N	0.6492	likely_pathogenic	0.7141	pathogenic	-1.122	Destabilizing	0.99	D	0.681	prob.neutral	None	None	None	None	N
E/P	0.7886	likely_pathogenic	0.7835	pathogenic	-0.209	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
E/Q	0.456	ambiguous	0.4231	ambiguous	-0.994	Destabilizing	0.997	D	0.629	neutral	D	0.524791486	None	None	N
E/R	0.8123	likely_pathogenic	0.7804	pathogenic	-0.48	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
E/S	0.6267	likely_pathogenic	0.6414	pathogenic	-1.45	Destabilizing	0.983	D	0.583	neutral	None	None	None	None	N
E/T	0.7207	likely_pathogenic	0.7312	pathogenic	-1.158	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
E/V	0.6375	likely_pathogenic	0.6436	pathogenic	-0.209	Destabilizing	0.997	D	0.747	deleterious	N	0.488729479	None	None	N
E/W	0.9917	likely_pathogenic	0.9928	pathogenic	-0.161	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/Y	0.9605	likely_pathogenic	0.966	pathogenic	-0.152	Destabilizing	1.0	D	0.743	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.