TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15359	46300;46301;46302	chr2:178620446;178620445;178620444	chr2:179485173;179485172;179485171
N2AB	13718	41377;41378;41379	chr2:178620446;178620445;178620444	chr2:179485173;179485172;179485171
N2A	12791	38596;38597;38598	chr2:178620446;178620445;178620444	chr2:179485173;179485172;179485171
N2B	6294	19105;19106;19107	chr2:178620446;178620445;178620444	chr2:179485173;179485172;179485171
Novex-1	6419	19480;19481;19482	chr2:178620446;178620445;178620444	chr2:179485173;179485172;179485171
Novex-2	6486	19681;19682;19683	chr2:178620446;178620445;178620444	chr2:179485173;179485172;179485171
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: Ig-105
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.2714
• 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/N	rs780024396	-1.058	0.741	N	0.52	0.215	0.307016933798	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
T/N	rs780024396	-1.058	0.741	N	0.52	0.215	0.307016933798	gnomAD-4.0.0	3.18866E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72833E-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	0.123	likely_benign	0.1273	benign	-1.002	Destabilizing	0.027	N	0.447	neutral	D	0.557084038	None	None	N
T/C	0.3989	ambiguous	0.4452	ambiguous	-0.845	Destabilizing	0.935	D	0.539	neutral	None	None	None	None	N
T/D	0.4806	ambiguous	0.5256	ambiguous	-0.682	Destabilizing	0.555	D	0.547	neutral	None	None	None	None	N
T/E	0.3377	likely_benign	0.3905	ambiguous	-0.637	Destabilizing	0.262	N	0.531	neutral	None	None	None	None	N
T/F	0.1852	likely_benign	0.2184	benign	-1.064	Destabilizing	0.38	N	0.575	neutral	None	None	None	None	N
T/G	0.3871	ambiguous	0.4098	ambiguous	-1.284	Destabilizing	0.262	N	0.547	neutral	None	None	None	None	N
T/H	0.2092	likely_benign	0.2404	benign	-1.559	Destabilizing	0.935	D	0.587	neutral	None	None	None	None	N
T/I	0.0817	likely_benign	0.1038	benign	-0.329	Destabilizing	None	N	0.337	neutral	N	0.437656235	None	None	N
T/K	0.2505	likely_benign	0.2693	benign	-0.732	Destabilizing	0.555	D	0.541	neutral	None	None	None	None	N
T/L	0.0851	likely_benign	0.0918	benign	-0.329	Destabilizing	0.005	N	0.405	neutral	None	None	None	None	N
T/M	0.0855	likely_benign	0.0939	benign	-0.055	Destabilizing	0.38	N	0.551	neutral	None	None	None	None	N
T/N	0.1342	likely_benign	0.1484	benign	-0.885	Destabilizing	0.741	D	0.52	neutral	N	0.510315526	None	None	N
T/P	0.7883	likely_pathogenic	0.7043	pathogenic	-0.522	Destabilizing	0.741	D	0.549	neutral	D	0.60221455	None	None	N
T/Q	0.2296	likely_benign	0.2568	benign	-1.042	Destabilizing	0.791	D	0.555	neutral	None	None	None	None	N
T/R	0.1897	likely_benign	0.1936	benign	-0.564	Destabilizing	0.555	D	0.543	neutral	None	None	None	None	N
T/S	0.1381	likely_benign	0.1534	benign	-1.174	Destabilizing	0.117	N	0.533	neutral	N	0.508173517	None	None	N
T/V	0.091	likely_benign	0.1105	benign	-0.522	Destabilizing	None	N	0.232	neutral	None	None	None	None	N
T/W	0.5244	ambiguous	0.5509	ambiguous	-0.986	Destabilizing	0.935	D	0.619	neutral	None	None	None	None	N
T/Y	0.2274	likely_benign	0.2544	benign	-0.714	Destabilizing	0.555	D	0.575	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.