TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27757	83494;83495;83496	chr2:178562863;178562862;178562861	chr2:179427590;179427589;179427588
N2AB	26116	78571;78572;78573	chr2:178562863;178562862;178562861	chr2:179427590;179427589;179427588
N2A	25189	75790;75791;75792	chr2:178562863;178562862;178562861	chr2:179427590;179427589;179427588
N2B	18692	56299;56300;56301	chr2:178562863;178562862;178562861	chr2:179427590;179427589;179427588
Novex-1	18817	56674;56675;56676	chr2:178562863;178562862;178562861	chr2:179427590;179427589;179427588
Novex-2	18884	56875;56876;56877	chr2:178562863;178562862;178562861	chr2:179427590;179427589;179427588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-141
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.2161
• 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
A/V	None	None	0.085	N	0.391	0.218	0.324436698001	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
A/C	0.7323	likely_pathogenic	0.7158	pathogenic	-0.768	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
A/D	0.9712	likely_pathogenic	0.9739	pathogenic	-0.504	Destabilizing	0.996	D	0.877	deleterious	D	0.543327365	None	None	N
A/E	0.9585	likely_pathogenic	0.9589	pathogenic	-0.523	Destabilizing	0.992	D	0.855	deleterious	None	None	None	None	N
A/F	0.8461	likely_pathogenic	0.8252	pathogenic	-0.691	Destabilizing	0.983	D	0.893	deleterious	None	None	None	None	N
A/G	0.4364	ambiguous	0.4312	ambiguous	-0.858	Destabilizing	0.963	D	0.613	neutral	N	0.515842007	None	None	N
A/H	0.9594	likely_pathogenic	0.961	pathogenic	-0.878	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
A/I	0.6384	likely_pathogenic	0.5979	pathogenic	-0.076	Destabilizing	0.745	D	0.755	deleterious	None	None	None	None	N
A/K	0.9799	likely_pathogenic	0.9828	pathogenic	-0.841	Destabilizing	0.992	D	0.856	deleterious	None	None	None	None	N
A/L	0.5888	likely_pathogenic	0.5709	pathogenic	-0.076	Destabilizing	0.895	D	0.596	neutral	None	None	None	None	N
A/M	0.6658	likely_pathogenic	0.6342	pathogenic	-0.224	Destabilizing	0.996	D	0.845	deleterious	None	None	None	None	N
A/N	0.9069	likely_pathogenic	0.9092	pathogenic	-0.645	Destabilizing	0.997	D	0.892	deleterious	None	None	None	None	N
A/P	0.9859	likely_pathogenic	0.9898	pathogenic	-0.21	Destabilizing	0.996	D	0.867	deleterious	D	0.544341323	None	None	N
A/Q	0.9223	likely_pathogenic	0.9241	pathogenic	-0.737	Destabilizing	0.997	D	0.867	deleterious	None	None	None	None	N
A/R	0.9534	likely_pathogenic	0.9599	pathogenic	-0.559	Destabilizing	0.992	D	0.869	deleterious	None	None	None	None	N
A/S	0.2723	likely_benign	0.2722	benign	-1.043	Destabilizing	0.928	D	0.623	neutral	N	0.512684272	None	None	N
A/T	0.3149	likely_benign	0.2966	benign	-0.946	Destabilizing	0.928	D	0.703	prob.neutral	N	0.492431187	None	None	N
A/V	0.3375	likely_benign	0.318	benign	-0.21	Destabilizing	0.085	N	0.391	neutral	N	0.503758144	None	None	N
A/W	0.9853	likely_pathogenic	0.9847	pathogenic	-1.016	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
A/Y	0.9276	likely_pathogenic	0.9247	pathogenic	-0.579	Destabilizing	0.992	D	0.892	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.