TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34989	105190;105191;105192	chr2:178531650;178531649;178531648	chr2:179396377;179396376;179396375
N2AB	33348	100267;100268;100269	chr2:178531650;178531649;178531648	chr2:179396377;179396376;179396375
N2A	32421	97486;97487;97488	chr2:178531650;178531649;178531648	chr2:179396377;179396376;179396375
N2B	25924	77995;77996;77997	chr2:178531650;178531649;178531648	chr2:179396377;179396376;179396375
Novex-1	26049	78370;78371;78372	chr2:178531650;178531649;178531648	chr2:179396377;179396376;179396375
Novex-2	26116	78571;78572;78573	chr2:178531650;178531649;178531648	chr2:179396377;179396376;179396375
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-163
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3854
• 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
H/R	rs1187175097	-0.931	None	N	0.105	0.097	0.107399877778	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
H/R	rs1187175097	-0.931	None	N	0.105	0.097	0.107399877778	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/R	rs1187175097	-0.931	None	N	0.105	0.097	0.107399877778	gnomAD-4.0.0	5.57655E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78034E-06	0	1.60087E-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
H/A	0.4984	ambiguous	0.5463	ambiguous	-0.885	Destabilizing	0.031	N	0.429	neutral	None	None	None	None	N
H/C	0.23	likely_benign	0.2174	benign	-0.205	Destabilizing	0.864	D	0.494	neutral	None	None	None	None	N
H/D	0.5277	ambiguous	0.61	pathogenic	-0.185	Destabilizing	0.055	N	0.4	neutral	N	0.496597312	None	None	N
H/E	0.5015	ambiguous	0.5533	ambiguous	-0.079	Destabilizing	0.038	N	0.289	neutral	None	None	None	None	N
H/F	0.48	ambiguous	0.5063	ambiguous	0.275	Stabilizing	0.038	N	0.354	neutral	None	None	None	None	N
H/G	0.5455	ambiguous	0.5924	pathogenic	-1.253	Destabilizing	0.072	N	0.445	neutral	None	None	None	None	N
H/I	0.4605	ambiguous	0.4708	ambiguous	0.13	Stabilizing	0.356	N	0.503	neutral	None	None	None	None	N
H/K	0.2761	likely_benign	0.2622	benign	-0.56	Destabilizing	0.016	N	0.392	neutral	None	None	None	None	N
H/L	0.2207	likely_benign	0.2407	benign	0.13	Stabilizing	0.055	N	0.488	neutral	N	0.461041943	None	None	N
H/M	0.6759	likely_pathogenic	0.6801	pathogenic	-0.069	Destabilizing	0.628	D	0.461	neutral	None	None	None	None	N
H/N	0.2203	likely_benign	0.2481	benign	-0.66	Destabilizing	0.055	N	0.306	neutral	N	0.480299708	None	None	N
H/P	0.839	likely_pathogenic	0.8899	pathogenic	-0.188	Destabilizing	0.295	N	0.468	neutral	N	0.516049864	None	None	N
H/Q	0.2306	likely_benign	0.233	benign	-0.433	Destabilizing	0.029	N	0.323	neutral	N	0.42094476	None	None	N
H/R	0.0788	likely_benign	0.0763	benign	-0.904	Destabilizing	None	N	0.105	neutral	N	0.417539095	None	None	N
H/S	0.3789	ambiguous	0.4236	ambiguous	-0.865	Destabilizing	0.072	N	0.399	neutral	None	None	None	None	N
H/T	0.3869	ambiguous	0.4169	ambiguous	-0.647	Destabilizing	0.072	N	0.431	neutral	None	None	None	None	N
H/V	0.4083	ambiguous	0.4184	ambiguous	-0.188	Destabilizing	0.072	N	0.479	neutral	None	None	None	None	N
H/W	0.4954	ambiguous	0.5024	ambiguous	0.658	Stabilizing	0.864	D	0.456	neutral	None	None	None	None	N
H/Y	0.1745	likely_benign	0.1796	benign	0.761	Stabilizing	None	N	0.107	neutral	N	0.468007988	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.