TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35135	105628;105629;105630	chr2:178531212;178531211;178531210	chr2:179395939;179395938;179395937
N2AB	33494	100705;100706;100707	chr2:178531212;178531211;178531210	chr2:179395939;179395938;179395937
N2A	32567	97924;97925;97926	chr2:178531212;178531211;178531210	chr2:179395939;179395938;179395937
N2B	26070	78433;78434;78435	chr2:178531212;178531211;178531210	chr2:179395939;179395938;179395937
Novex-1	26195	78808;78809;78810	chr2:178531212;178531211;178531210	chr2:179395939;179395938;179395937
Novex-2	26262	79009;79010;79011	chr2:178531212;178531211;178531210	chr2:179395939;179395938;179395937
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-164
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1307
• 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/L	rs1575228534	None	1.0	N	0.895	0.443	0.384919354899	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85755E-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	0.6942	likely_pathogenic	0.8015	pathogenic	-1.356	Destabilizing	1.0	D	0.783	deleterious	N	0.510315105	None	None	N
P/C	0.9904	likely_pathogenic	0.9928	pathogenic	-0.816	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/D	0.9964	likely_pathogenic	0.999	pathogenic	-1.423	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/E	0.9884	likely_pathogenic	0.997	pathogenic	-1.191	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/F	0.9952	likely_pathogenic	0.9981	pathogenic	-0.692	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/G	0.9686	likely_pathogenic	0.9835	pathogenic	-1.898	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/H	0.9908	likely_pathogenic	0.9974	pathogenic	-1.716	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/I	0.9573	likely_pathogenic	0.9744	pathogenic	0.144	Stabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/K	0.9933	likely_pathogenic	0.9983	pathogenic	-0.802	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/L	0.8405	likely_pathogenic	0.8792	pathogenic	0.144	Stabilizing	1.0	D	0.895	deleterious	N	0.505807788	None	None	N
P/M	0.9737	likely_pathogenic	0.9835	pathogenic	-0.003	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/N	0.9932	likely_pathogenic	0.9977	pathogenic	-1.117	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/Q	0.9778	likely_pathogenic	0.9936	pathogenic	-0.886	Destabilizing	1.0	D	0.887	deleterious	N	0.474257804	None	None	N
P/R	0.9838	likely_pathogenic	0.9957	pathogenic	-0.938	Destabilizing	1.0	D	0.901	deleterious	N	0.489399544	None	None	N
P/S	0.9489	likely_pathogenic	0.9811	pathogenic	-1.784	Destabilizing	1.0	D	0.849	deleterious	N	0.512643334	None	None	N
P/T	0.9143	likely_pathogenic	0.962	pathogenic	-1.388	Destabilizing	1.0	D	0.867	deleterious	N	0.47078831	None	None	N
P/V	0.9041	likely_pathogenic	0.9345	pathogenic	-0.326	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/W	0.9989	likely_pathogenic	0.9997	pathogenic	-1.162	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/Y	0.9969	likely_pathogenic	0.9991	pathogenic	-0.679	Destabilizing	1.0	D	0.885	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.