TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2625	8098;8099;8100	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179
N2AB	2625	8098;8099;8100	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179
N2A	2625	8098;8099;8100	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179
N2B	2579	7960;7961;7962	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179
Novex-1	2579	7960;7961;7962	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179
Novex-2	2579	7960;7961;7962	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179
Novex-3	2625	8098;8099;8100	chr2:178771454;178771453;178771452	chr2:179636181;179636180;179636179

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-16
• Domain position: 5
• Structural Position: 7
• Q(SASA): 0.4433
• 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
P/S	None	None	1.0	D	0.824	0.46	0.444807159249	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.1511	likely_benign	0.153	benign	-0.975	Destabilizing	1.0	D	0.76	deleterious	D	0.571733012	None	None	N
P/C	0.8031	likely_pathogenic	0.8032	pathogenic	-0.672	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/D	0.7432	likely_pathogenic	0.7285	pathogenic	-0.577	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/E	0.5329	ambiguous	0.5267	ambiguous	-0.649	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/F	0.7367	likely_pathogenic	0.7454	pathogenic	-0.918	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
P/G	0.576	likely_pathogenic	0.568	pathogenic	-1.193	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/H	0.3933	ambiguous	0.3828	ambiguous	-0.733	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
P/I	0.5051	ambiguous	0.5339	ambiguous	-0.519	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/K	0.4624	ambiguous	0.4602	ambiguous	-0.78	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/L	0.2388	likely_benign	0.2445	benign	-0.519	Destabilizing	1.0	D	0.795	deleterious	D	0.592926914	None	None	N
P/M	0.5095	ambiguous	0.5245	ambiguous	-0.41	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
P/N	0.6157	likely_pathogenic	0.6058	pathogenic	-0.489	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/Q	0.2998	likely_benign	0.3045	benign	-0.723	Destabilizing	1.0	D	0.795	deleterious	D	0.571579235	None	None	N
P/R	0.3224	likely_benign	0.3228	benign	-0.244	Destabilizing	1.0	D	0.773	deleterious	D	0.568238386	None	None	N
P/S	0.2929	likely_benign	0.2933	benign	-0.936	Destabilizing	1.0	D	0.824	deleterious	D	0.584926552	None	None	N
P/T	0.2235	likely_benign	0.2293	benign	-0.907	Destabilizing	1.0	D	0.821	deleterious	D	0.562362129	None	None	N
P/V	0.3633	ambiguous	0.3831	ambiguous	-0.634	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/W	0.8846	likely_pathogenic	0.8908	pathogenic	-1.023	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
P/Y	0.6627	likely_pathogenic	0.6665	pathogenic	-0.737	Destabilizing	1.0	D	0.736	prob.delet.	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.