TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29738	89437;89438;89439	chr2:178553793;178553792;178553791	chr2:179418520;179418519;179418518
N2AB	28097	84514;84515;84516	chr2:178553793;178553792;178553791	chr2:179418520;179418519;179418518
N2A	27170	81733;81734;81735	chr2:178553793;178553792;178553791	chr2:179418520;179418519;179418518
N2B	20673	62242;62243;62244	chr2:178553793;178553792;178553791	chr2:179418520;179418519;179418518
Novex-1	20798	62617;62618;62619	chr2:178553793;178553792;178553791	chr2:179418520;179418519;179418518
Novex-2	20865	62818;62819;62820	chr2:178553793;178553792;178553791	chr2:179418520;179418519;179418518
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-105
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1095
• 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	0.852	0.712	0.658657864366	gnomAD-4.0.0	4.15042E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.53313E-06	0	1.67661E-05

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	0.6022	likely_pathogenic	0.682	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.579332511	None	None	N
P/C	0.9479	likely_pathogenic	0.9692	pathogenic	-2.146	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/D	0.9982	likely_pathogenic	0.9986	pathogenic	-3.233	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/E	0.9948	likely_pathogenic	0.9954	pathogenic	-3.013	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/F	0.9974	likely_pathogenic	0.9972	pathogenic	-1.33	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/G	0.981	likely_pathogenic	0.9876	pathogenic	-2.902	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/H	0.9938	likely_pathogenic	0.995	pathogenic	-2.56	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.63960424	None	None	N
P/I	0.8712	likely_pathogenic	0.8571	pathogenic	-0.855	Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
P/K	0.996	likely_pathogenic	0.9967	pathogenic	-2.005	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/L	0.7762	likely_pathogenic	0.7691	pathogenic	-0.855	Destabilizing	1.0	D	0.909	deleterious	D	0.622949106	None	None	N
P/M	0.9618	likely_pathogenic	0.9624	pathogenic	-1.099	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/N	0.9966	likely_pathogenic	0.9974	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/Q	0.9892	likely_pathogenic	0.9914	pathogenic	-2.23	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/R	0.9884	likely_pathogenic	0.9911	pathogenic	-1.788	Destabilizing	1.0	D	0.923	deleterious	D	0.639402435	None	None	N
P/S	0.952	likely_pathogenic	0.9696	pathogenic	-2.974	Highly Destabilizing	1.0	D	0.852	deleterious	D	0.61366252	None	None	N
P/T	0.8443	likely_pathogenic	0.8964	pathogenic	-2.615	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.639402435	None	None	N
P/V	0.6984	likely_pathogenic	0.6978	pathogenic	-1.334	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9996	pathogenic	-1.848	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/Y	0.9986	likely_pathogenic	0.9986	pathogenic	-1.535	Destabilizing	1.0	D	0.923	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.