TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7044	21355;21356;21357	chr2:178724129;178724128;178724127	chr2:179588856;179588855;179588854
N2AB	6727	20404;20405;20406	chr2:178724129;178724128;178724127	chr2:179588856;179588855;179588854
N2A	5800	17623;17624;17625	chr2:178724129;178724128;178724127	chr2:179588856;179588855;179588854
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-55
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1895
• 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	rs773899102	-1.631	0.322	D	0.675	0.754	0.477685322099	gnomAD-2.1.1	8.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
P/S	rs773899102	-1.631	0.322	D	0.675	0.754	0.477685322099	gnomAD-4.0.0	6.85243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00607E-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	0.703	likely_pathogenic	0.6568	pathogenic	-1.466	Destabilizing	0.885	D	0.717	prob.delet.	D	0.641854447	None	None	N
P/C	0.9778	likely_pathogenic	0.9793	pathogenic	-1.361	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
P/D	0.9981	likely_pathogenic	0.9987	pathogenic	-1.402	Destabilizing	0.986	D	0.794	deleterious	None	None	None	None	N
P/E	0.9935	likely_pathogenic	0.9952	pathogenic	-1.43	Destabilizing	0.986	D	0.804	deleterious	None	None	None	None	N
P/F	0.9957	likely_pathogenic	0.996	pathogenic	-1.448	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
P/G	0.9822	likely_pathogenic	0.9828	pathogenic	-1.724	Destabilizing	0.91	D	0.803	deleterious	None	None	None	None	N
P/H	0.9904	likely_pathogenic	0.9922	pathogenic	-1.202	Destabilizing	0.999	D	0.827	deleterious	D	0.658711386	None	None	N
P/I	0.9233	likely_pathogenic	0.945	pathogenic	-0.866	Destabilizing	0.386	N	0.759	deleterious	None	None	None	None	N
P/K	0.9948	likely_pathogenic	0.9966	pathogenic	-1.044	Destabilizing	0.986	D	0.799	deleterious	None	None	None	None	N
P/L	0.8532	likely_pathogenic	0.8622	pathogenic	-0.866	Destabilizing	0.885	D	0.806	deleterious	D	0.642258056	None	None	N
P/M	0.9841	likely_pathogenic	0.9856	pathogenic	-0.766	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
P/N	0.9962	likely_pathogenic	0.9972	pathogenic	-0.908	Destabilizing	0.986	D	0.821	deleterious	None	None	None	None	N
P/Q	0.9847	likely_pathogenic	0.9877	pathogenic	-1.17	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
P/R	0.9783	likely_pathogenic	0.9835	pathogenic	-0.53	Destabilizing	0.982	D	0.833	deleterious	D	0.658711386	None	None	N
P/S	0.9519	likely_pathogenic	0.952	pathogenic	-1.438	Destabilizing	0.322	N	0.675	prob.neutral	D	0.642056251	None	None	N
P/T	0.9278	likely_pathogenic	0.9351	pathogenic	-1.36	Destabilizing	0.885	D	0.783	deleterious	D	0.658509581	None	None	N
P/V	0.8269	likely_pathogenic	0.8556	pathogenic	-1.033	Destabilizing	0.91	D	0.781	deleterious	None	None	None	None	N
P/W	0.999	likely_pathogenic	0.9992	pathogenic	-1.53	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
P/Y	0.9974	likely_pathogenic	0.9976	pathogenic	-1.21	Destabilizing	0.998	D	0.844	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.