TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1590	4993;4994;4995	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920
N2AB	1590	4993;4994;4995	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920
N2A	1590	4993;4994;4995	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920
N2B	1544	4855;4856;4857	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920
Novex-1	1544	4855;4856;4857	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920
Novex-2	1544	4855;4856;4857	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920
Novex-3	1590	4993;4994;4995	chr2:178777195;178777194;178777193	chr2:179641922;179641921;179641920

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-7
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1072
• 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/F	None	None	0.988	N	0.763	0.213	0.477762074677	gnomAD-4.0.0	1.23138E-05	None	None	None	None	N	None	2.98757E-05	0	None	0	0	None	0	0	1.52886E-05	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	0.9829	likely_pathogenic	0.9721	pathogenic	-2.288	Highly Destabilizing	0.938	D	0.567	neutral	None	None	None	None	N
L/C	0.9823	likely_pathogenic	0.9729	pathogenic	-1.975	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9991	pathogenic	-1.807	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
L/E	0.9927	likely_pathogenic	0.987	pathogenic	-1.674	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
L/F	0.9287	likely_pathogenic	0.8751	pathogenic	-1.509	Destabilizing	0.988	D	0.763	deleterious	N	0.446616518	None	None	N
L/G	0.994	likely_pathogenic	0.9909	pathogenic	-2.736	Highly Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
L/H	0.9853	likely_pathogenic	0.9735	pathogenic	-1.911	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/I	0.6931	likely_pathogenic	0.6052	pathogenic	-1.05	Destabilizing	0.938	D	0.517	neutral	None	None	None	None	N
L/K	0.9728	likely_pathogenic	0.9577	pathogenic	-1.556	Destabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
L/M	0.5926	likely_pathogenic	0.4674	ambiguous	-1.15	Destabilizing	0.994	D	0.785	deleterious	N	0.468782313	None	None	N
L/N	0.9937	likely_pathogenic	0.9887	pathogenic	-1.657	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
L/P	0.9997	likely_pathogenic	0.9995	pathogenic	-1.438	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
L/Q	0.9663	likely_pathogenic	0.9363	pathogenic	-1.683	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
L/R	0.9622	likely_pathogenic	0.9458	pathogenic	-1.138	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/S	0.9962	likely_pathogenic	0.9921	pathogenic	-2.477	Highly Destabilizing	0.994	D	0.747	deleterious	N	0.447437556	None	None	N
L/T	0.986	likely_pathogenic	0.9733	pathogenic	-2.203	Highly Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	N
L/V	0.8016	likely_pathogenic	0.7205	pathogenic	-1.438	Destabilizing	0.067	N	0.364	neutral	N	0.482904581	None	None	N
L/W	0.9812	likely_pathogenic	0.9677	pathogenic	-1.629	Destabilizing	0.999	D	0.79	deleterious	D	0.539406131	None	None	N
L/Y	0.9813	likely_pathogenic	0.9664	pathogenic	-1.383	Destabilizing	0.995	D	0.795	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.