TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4635	14128;14129;14130	chr2:178739330;178739329;178739328	chr2:179604057;179604056;179604055
N2AB	4318	13177;13178;13179	chr2:178739330;178739329;178739328	chr2:179604057;179604056;179604055
N2A	None	None	chr2:None	chr2:None
N2B	4272	13039;13040;13041	chr2:178739330;178739329;178739328	chr2:179604057;179604056;179604055
Novex-1	4397	13414;13415;13416	chr2:178739330;178739329;178739328	chr2:179604057;179604056;179604055
Novex-2	4464	13615;13616;13617	chr2:178739330;178739329;178739328	chr2:179604057;179604056;179604055
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-29
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.1408
• 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
V/A	None	None	0.977	D	0.579	0.685	None	gnomAD-4.0.0	4.10548E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39683E-06	0	0
V/M	None	None	0.993	D	0.76	0.594	None	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
V/A	0.5169	ambiguous	0.5305	ambiguous	-1.767	Destabilizing	0.977	D	0.579	neutral	D	0.679847732	None	None	N
V/C	0.8951	likely_pathogenic	0.9013	pathogenic	-1.048	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/D	0.9401	likely_pathogenic	0.9542	pathogenic	-1.974	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
V/E	0.8789	likely_pathogenic	0.9016	pathogenic	-1.845	Destabilizing	0.999	D	0.857	deleterious	D	0.76505727	None	None	N
V/F	0.5669	likely_pathogenic	0.5944	pathogenic	-1.18	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
V/G	0.5804	likely_pathogenic	0.6085	pathogenic	-2.214	Highly Destabilizing	0.999	D	0.88	deleterious	D	0.76505727	None	None	N
V/H	0.9672	likely_pathogenic	0.9738	pathogenic	-1.895	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1192	likely_benign	0.1173	benign	-0.568	Destabilizing	0.15	N	0.231	neutral	None	None	None	None	N
V/K	0.8788	likely_pathogenic	0.9099	pathogenic	-1.406	Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	N
V/L	0.6128	likely_pathogenic	0.6517	pathogenic	-0.568	Destabilizing	0.898	D	0.593	neutral	D	0.655149321	None	None	N
V/M	0.4244	ambiguous	0.469	ambiguous	-0.398	Destabilizing	0.993	D	0.76	deleterious	D	0.76531041	None	None	N
V/N	0.8575	likely_pathogenic	0.8868	pathogenic	-1.414	Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
V/P	0.9497	likely_pathogenic	0.9538	pathogenic	-0.937	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
V/Q	0.907	likely_pathogenic	0.9265	pathogenic	-1.406	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
V/R	0.8583	likely_pathogenic	0.8913	pathogenic	-1.102	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
V/S	0.77	likely_pathogenic	0.7978	pathogenic	-1.981	Destabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
V/T	0.6028	likely_pathogenic	0.6461	pathogenic	-1.721	Destabilizing	0.983	D	0.685	prob.neutral	None	None	None	None	N
V/W	0.9688	likely_pathogenic	0.9745	pathogenic	-1.583	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/Y	0.8884	likely_pathogenic	0.9069	pathogenic	-1.208	Destabilizing	0.999	D	0.803	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.