TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24612	74059;74060;74061	chr2:178572298;178572297;178572296	chr2:179437025;179437024;179437023
N2AB	22971	69136;69137;69138	chr2:178572298;178572297;178572296	chr2:179437025;179437024;179437023
N2A	22044	66355;66356;66357	chr2:178572298;178572297;178572296	chr2:179437025;179437024;179437023
N2B	15547	46864;46865;46866	chr2:178572298;178572297;178572296	chr2:179437025;179437024;179437023
Novex-1	15672	47239;47240;47241	chr2:178572298;178572297;178572296	chr2:179437025;179437024;179437023
Novex-2	15739	47440;47441;47442	chr2:178572298;178572297;178572296	chr2:179437025;179437024;179437023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-66
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.1775
• 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
K/T	None	None	0.198	N	0.424	0.124	0.184867976434	gnomAD-4.0.0	1.59559E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86906E-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
K/A	0.909	likely_pathogenic	0.8244	pathogenic	-0.074	Destabilizing	0.988	D	0.555	neutral	None	None	None	None	N
K/C	0.938	likely_pathogenic	0.8939	pathogenic	-0.281	Destabilizing	1.0	D	0.723	deleterious	None	None	None	None	N
K/D	0.9875	likely_pathogenic	0.975	pathogenic	0.259	Stabilizing	0.998	D	0.557	neutral	None	None	None	None	N
K/E	0.8869	likely_pathogenic	0.7789	pathogenic	0.253	Stabilizing	0.974	D	0.545	neutral	N	0.469906619	None	None	N
K/F	0.9716	likely_pathogenic	0.9418	pathogenic	-0.41	Destabilizing	0.999	D	0.722	deleterious	None	None	None	None	N
K/G	0.9694	likely_pathogenic	0.9333	pathogenic	-0.242	Destabilizing	0.998	D	0.447	neutral	None	None	None	None	N
K/H	0.751	likely_pathogenic	0.6298	pathogenic	-0.573	Destabilizing	1.0	D	0.674	prob.neutral	None	None	None	None	N
K/I	0.7182	likely_pathogenic	0.5989	pathogenic	0.28	Stabilizing	0.863	D	0.721	deleterious	N	0.511568685	None	None	N
K/L	0.7327	likely_pathogenic	0.6032	pathogenic	0.28	Stabilizing	0.705	D	0.515	neutral	None	None	None	None	N
K/M	0.6726	likely_pathogenic	0.532	ambiguous	0.224	Stabilizing	0.999	D	0.659	prob.neutral	None	None	None	None	N
K/N	0.9611	likely_pathogenic	0.9214	pathogenic	0.264	Stabilizing	0.998	D	0.599	neutral	N	0.483491423	None	None	N
K/P	0.9642	likely_pathogenic	0.9396	pathogenic	0.188	Stabilizing	0.999	D	0.642	neutral	None	None	None	None	N
K/Q	0.5438	ambiguous	0.3931	ambiguous	0.043	Stabilizing	0.994	D	0.631	neutral	N	0.460778812	None	None	N
K/R	0.1125	likely_benign	0.0921	benign	0.052	Stabilizing	0.958	D	0.619	neutral	N	0.499620895	None	None	N
K/S	0.9627	likely_pathogenic	0.9197	pathogenic	-0.291	Destabilizing	0.976	D	0.509	neutral	None	None	None	None	N
K/T	0.6989	likely_pathogenic	0.5434	ambiguous	-0.153	Destabilizing	0.198	N	0.424	neutral	N	0.460048495	None	None	N
K/V	0.6939	likely_pathogenic	0.5772	pathogenic	0.188	Stabilizing	0.917	D	0.455	neutral	None	None	None	None	N
K/W	0.9653	likely_pathogenic	0.9271	pathogenic	-0.39	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
K/Y	0.945	likely_pathogenic	0.9025	pathogenic	-0.014	Destabilizing	0.988	D	0.728	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.