TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29460	88603;88604;88605	chr2:178555081;178555080;178555079	chr2:179419808;179419807;179419806
N2AB	27819	83680;83681;83682	chr2:178555081;178555080;178555079	chr2:179419808;179419807;179419806
N2A	26892	80899;80900;80901	chr2:178555081;178555080;178555079	chr2:179419808;179419807;179419806
N2B	20395	61408;61409;61410	chr2:178555081;178555080;178555079	chr2:179419808;179419807;179419806
Novex-1	20520	61783;61784;61785	chr2:178555081;178555080;178555079	chr2:179419808;179419807;179419806
Novex-2	20587	61984;61985;61986	chr2:178555081;178555080;178555079	chr2:179419808;179419807;179419806
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-146
• Domain position: 17
• Structural Position: 30
• Q(SASA): 0.1522
• 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
L/I	None	None	0.884	D	0.345	0.329	0.624915994163	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85793E-06	0	0
L/P	rs1273946474	None	1.0	D	0.893	0.881	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs1273946474	None	1.0	D	0.893	0.881	None	gnomAD-4.0.0	6.57134E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	0	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
L/A	0.9718	likely_pathogenic	0.9665	pathogenic	-1.609	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
L/C	0.9543	likely_pathogenic	0.948	pathogenic	-1.263	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9989	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/E	0.9943	likely_pathogenic	0.9939	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/F	0.5052	ambiguous	0.4448	ambiguous	-1.168	Destabilizing	0.999	D	0.781	deleterious	D	0.527152292	None	None	N
L/G	0.9928	likely_pathogenic	0.9911	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/H	0.9875	likely_pathogenic	0.9858	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.599200462	None	None	N
L/I	0.1319	likely_benign	0.1258	benign	-0.278	Destabilizing	0.884	D	0.345	neutral	D	0.55897489	None	None	N
L/K	0.9877	likely_pathogenic	0.9875	pathogenic	-1.387	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/M	0.3105	likely_benign	0.2902	benign	-0.583	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/N	0.9961	likely_pathogenic	0.9957	pathogenic	-2.005	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/P	0.992	likely_pathogenic	0.9894	pathogenic	-0.713	Destabilizing	1.0	D	0.893	deleterious	D	0.599200462	None	None	N
L/Q	0.9824	likely_pathogenic	0.9792	pathogenic	-1.629	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/R	0.9812	likely_pathogenic	0.979	pathogenic	-1.751	Destabilizing	1.0	D	0.889	deleterious	D	0.599200462	None	None	N
L/S	0.9966	likely_pathogenic	0.9957	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/T	0.9864	likely_pathogenic	0.9844	pathogenic	-1.973	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
L/V	0.2976	likely_benign	0.2756	benign	-0.713	Destabilizing	0.981	D	0.649	neutral	D	0.552919333	None	None	N
L/W	0.9067	likely_pathogenic	0.8844	pathogenic	-1.502	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9382	likely_pathogenic	0.9238	pathogenic	-1.232	Destabilizing	1.0	D	0.833	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.