TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24946	75061;75062;75063	chr2:178571296;178571295;178571294	chr2:179436023;179436022;179436021
N2AB	23305	70138;70139;70140	chr2:178571296;178571295;178571294	chr2:179436023;179436022;179436021
N2A	22378	67357;67358;67359	chr2:178571296;178571295;178571294	chr2:179436023;179436022;179436021
N2B	15881	47866;47867;47868	chr2:178571296;178571295;178571294	chr2:179436023;179436022;179436021
Novex-1	16006	48241;48242;48243	chr2:178571296;178571295;178571294	chr2:179436023;179436022;179436021
Novex-2	16073	48442;48443;48444	chr2:178571296;178571295;178571294	chr2:179436023;179436022;179436021
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-69
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1537
• 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
E/K	rs758242306	-1.014	0.998	N	0.663	0.394	0.401185642668	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs758242306	-1.014	0.998	N	0.663	0.394	0.401185642668	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/K	rs758242306	-1.014	0.998	N	0.663	0.394	0.401185642668	gnomAD-4.0.0	6.57817E-06	None	None	None	None	N	None	0	6.55738E-05	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
E/A	0.7662	likely_pathogenic	0.7851	pathogenic	-1.431	Destabilizing	0.998	D	0.688	prob.neutral	D	0.536178935	None	None	N
E/C	0.9609	likely_pathogenic	0.9637	pathogenic	-0.681	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.6853	likely_pathogenic	0.6163	pathogenic	-1.715	Destabilizing	0.434	N	0.342	neutral	N	0.48409467	None	None	N
E/F	0.9507	likely_pathogenic	0.9545	pathogenic	-1.052	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/G	0.8645	likely_pathogenic	0.8717	pathogenic	-1.835	Destabilizing	0.999	D	0.76	deleterious	D	0.549474252	None	None	N
E/H	0.8981	likely_pathogenic	0.9013	pathogenic	-0.986	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/I	0.9036	likely_pathogenic	0.9054	pathogenic	-0.267	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/K	0.8941	likely_pathogenic	0.9019	pathogenic	-1.466	Destabilizing	0.998	D	0.663	neutral	N	0.512198877	None	None	N
E/L	0.8785	likely_pathogenic	0.8852	pathogenic	-0.267	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/M	0.8835	likely_pathogenic	0.895	pathogenic	0.455	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/N	0.9343	likely_pathogenic	0.9333	pathogenic	-1.725	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9995	pathogenic	-0.641	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Q	0.3943	ambiguous	0.4276	ambiguous	-1.419	Destabilizing	0.999	D	0.75	deleterious	N	0.476141725	None	None	N
E/R	0.9087	likely_pathogenic	0.9136	pathogenic	-1.303	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/S	0.7901	likely_pathogenic	0.7945	pathogenic	-2.352	Highly Destabilizing	0.997	D	0.675	prob.neutral	None	None	None	None	N
E/T	0.8935	likely_pathogenic	0.8944	pathogenic	-1.969	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/V	0.8046	likely_pathogenic	0.8056	pathogenic	-0.641	Destabilizing	1.0	D	0.802	deleterious	D	0.536939404	None	None	N
E/W	0.9785	likely_pathogenic	0.9793	pathogenic	-1.132	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/Y	0.9386	likely_pathogenic	0.9401	pathogenic	-0.864	Destabilizing	1.0	D	0.834	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.