TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33496	100711;100712;100713	chr2:178536261;178536260;178536259	chr2:179400988;179400987;179400986
N2AB	31855	95788;95789;95790	chr2:178536261;178536260;178536259	chr2:179400988;179400987;179400986
N2A	30928	93007;93008;93009	chr2:178536261;178536260;178536259	chr2:179400988;179400987;179400986
N2B	24431	73516;73517;73518	chr2:178536261;178536260;178536259	chr2:179400988;179400987;179400986
Novex-1	24556	73891;73892;73893	chr2:178536261;178536260;178536259	chr2:179400988;179400987;179400986
Novex-2	24623	74092;74093;74094	chr2:178536261;178536260;178536259	chr2:179400988;179400987;179400986
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-158
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1571
• 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/T	rs1691443829	None	1.0	D	0.898	0.724	0.763848737128	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85881E-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	0.8505	likely_pathogenic	0.8822	pathogenic	-1.667	Destabilizing	1.0	D	0.833	deleterious	D	0.629128215	None	None	N
P/C	0.9896	likely_pathogenic	0.9929	pathogenic	-1.597	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9996	pathogenic	-2.134	Highly Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
P/E	0.9981	likely_pathogenic	0.9989	pathogenic	-2.113	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9996	pathogenic	-1.458	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/G	0.9914	likely_pathogenic	0.9927	pathogenic	-1.987	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/H	0.9981	likely_pathogenic	0.9989	pathogenic	-1.474	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/I	0.9855	likely_pathogenic	0.9915	pathogenic	-0.867	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.9993	pathogenic	-1.282	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/L	0.9668	likely_pathogenic	0.9785	pathogenic	-0.867	Destabilizing	1.0	D	0.893	deleterious	D	0.617691426	None	None	N
P/M	0.996	likely_pathogenic	0.9975	pathogenic	-0.84	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/N	0.9986	likely_pathogenic	0.9992	pathogenic	-1.273	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/Q	0.9964	likely_pathogenic	0.998	pathogenic	-1.488	Destabilizing	1.0	D	0.894	deleterious	D	0.639625626	None	None	N
P/R	0.9951	likely_pathogenic	0.997	pathogenic	-0.783	Destabilizing	1.0	D	0.897	deleterious	D	0.655877152	None	None	N
P/S	0.9807	likely_pathogenic	0.9887	pathogenic	-1.792	Destabilizing	1.0	D	0.901	deleterious	D	0.655473543	None	None	N
P/T	0.9758	likely_pathogenic	0.9868	pathogenic	-1.662	Destabilizing	1.0	D	0.898	deleterious	D	0.639423822	None	None	N
P/V	0.9576	likely_pathogenic	0.9729	pathogenic	-1.102	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.65	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9997	pathogenic	-1.321	Destabilizing	1.0	D	0.893	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.