TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3000	9223;9224;9225	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563
N2AB	3000	9223;9224;9225	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563
N2A	3000	9223;9224;9225	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563
N2B	2954	9085;9086;9087	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563
Novex-1	2954	9085;9086;9087	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563
Novex-2	2954	9085;9086;9087	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563
Novex-3	3000	9223;9224;9225	chr2:178768838;178768837;178768836	chr2:179633565;179633564;179633563

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-20
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.2818
• 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
K/R	None	None	0.999	N	0.593	0.416	0.314417295294	gnomAD-4.0.0	1.59063E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85651E-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
K/A	0.8031	likely_pathogenic	0.8194	pathogenic	-0.881	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
K/C	0.8861	likely_pathogenic	0.9022	pathogenic	-0.951	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/D	0.957	likely_pathogenic	0.9586	pathogenic	-0.725	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/E	0.5895	likely_pathogenic	0.596	pathogenic	-0.498	Destabilizing	0.999	D	0.613	neutral	N	0.506124759	None	None	N
K/F	0.9711	likely_pathogenic	0.9747	pathogenic	-0.258	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
K/G	0.9195	likely_pathogenic	0.9229	pathogenic	-1.318	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/H	0.5314	ambiguous	0.5538	ambiguous	-1.202	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/I	0.712	likely_pathogenic	0.7403	pathogenic	0.314	Stabilizing	1.0	D	0.845	deleterious	D	0.552277136	None	None	N
K/L	0.733	likely_pathogenic	0.7443	pathogenic	0.314	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/M	0.5804	likely_pathogenic	0.614	pathogenic	-0.095	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/N	0.831	likely_pathogenic	0.8445	pathogenic	-1.096	Destabilizing	1.0	D	0.757	deleterious	D	0.591784175	None	None	N
K/P	0.9956	likely_pathogenic	0.9951	pathogenic	-0.058	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
K/Q	0.2464	likely_benign	0.2541	benign	-0.905	Destabilizing	1.0	D	0.757	deleterious	N	0.505432155	None	None	N
K/R	0.1081	likely_benign	0.1091	benign	-0.526	Destabilizing	0.999	D	0.593	neutral	N	0.500266614	None	None	N
K/S	0.7921	likely_pathogenic	0.8067	pathogenic	-1.698	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
K/T	0.4039	ambiguous	0.4234	ambiguous	-1.231	Destabilizing	1.0	D	0.776	deleterious	N	0.506989142	None	None	N
K/V	0.6641	likely_pathogenic	0.6877	pathogenic	-0.058	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/W	0.9646	likely_pathogenic	0.969	pathogenic	-0.224	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/Y	0.9138	likely_pathogenic	0.9261	pathogenic	0.091	Stabilizing	1.0	D	0.799	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.