TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19645	59158;59159;59160	chr2:178593275;178593274;178593273	chr2:179458002;179458001;179458000
N2AB	18004	54235;54236;54237	chr2:178593275;178593274;178593273	chr2:179458002;179458001;179458000
N2A	17077	51454;51455;51456	chr2:178593275;178593274;178593273	chr2:179458002;179458001;179458000
N2B	10580	31963;31964;31965	chr2:178593275;178593274;178593273	chr2:179458002;179458001;179458000
Novex-1	10705	32338;32339;32340	chr2:178593275;178593274;178593273	chr2:179458002;179458001;179458000
Novex-2	10772	32539;32540;32541	chr2:178593275;178593274;178593273	chr2:179458002;179458001;179458000
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-30
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6468
• 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	0.464	N	0.35	0.178	0.241664281697	gnomAD-4.0.0	6.84357E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99611E-07	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	0.3729	ambiguous	0.368	ambiguous	-1.025	Destabilizing	0.769	D	0.532	neutral	None	None	None	None	N
L/C	0.7121	likely_pathogenic	0.6927	pathogenic	-0.726	Destabilizing	0.994	D	0.659	neutral	None	None	None	None	N
L/D	0.8592	likely_pathogenic	0.845	pathogenic	-0.161	Destabilizing	0.979	D	0.707	prob.neutral	None	None	None	None	N
L/E	0.5679	likely_pathogenic	0.5302	ambiguous	-0.194	Destabilizing	0.979	D	0.696	prob.neutral	None	None	None	None	N
L/F	0.3173	likely_benign	0.2981	benign	-0.731	Destabilizing	0.959	D	0.689	prob.neutral	None	None	None	None	N
L/G	0.7329	likely_pathogenic	0.7262	pathogenic	-1.276	Destabilizing	0.979	D	0.695	prob.neutral	None	None	None	None	N
L/H	0.4361	ambiguous	0.4027	ambiguous	-0.373	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	N
L/I	0.1258	likely_benign	0.1164	benign	-0.446	Destabilizing	0.464	N	0.35	neutral	N	0.423955275	None	None	N
L/K	0.4349	ambiguous	0.4012	ambiguous	-0.513	Destabilizing	0.979	D	0.682	prob.neutral	None	None	None	None	N
L/M	0.159	likely_benign	0.1477	benign	-0.487	Destabilizing	0.959	D	0.666	neutral	None	None	None	None	N
L/N	0.6028	likely_pathogenic	0.595	pathogenic	-0.324	Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	N
L/P	0.7328	likely_pathogenic	0.6952	pathogenic	-0.606	Destabilizing	0.991	D	0.713	prob.delet.	N	0.504397571	None	None	N
L/Q	0.2652	likely_benign	0.2359	benign	-0.488	Destabilizing	0.991	D	0.701	prob.neutral	N	0.464588389	None	None	N
L/R	0.3587	ambiguous	0.3326	benign	0.031	Stabilizing	0.973	D	0.706	prob.neutral	N	0.465164392	None	None	N
L/S	0.5044	ambiguous	0.4894	ambiguous	-0.921	Destabilizing	0.959	D	0.684	prob.neutral	None	None	None	None	N
L/T	0.3055	likely_benign	0.2911	benign	-0.83	Destabilizing	0.959	D	0.652	neutral	None	None	None	None	N
L/V	0.1388	likely_benign	0.1249	benign	-0.606	Destabilizing	0.016	N	0.323	neutral	N	0.432150683	None	None	N
L/W	0.4261	ambiguous	0.4014	ambiguous	-0.736	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
L/Y	0.5344	ambiguous	0.526	ambiguous	-0.504	Destabilizing	0.979	D	0.717	prob.delet.	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.