TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25760	77503;77504;77505	chr2:178568854;178568853;178568852	chr2:179433581;179433580;179433579
N2AB	24119	72580;72581;72582	chr2:178568854;178568853;178568852	chr2:179433581;179433580;179433579
N2A	23192	69799;69800;69801	chr2:178568854;178568853;178568852	chr2:179433581;179433580;179433579
N2B	16695	50308;50309;50310	chr2:178568854;178568853;178568852	chr2:179433581;179433580;179433579
Novex-1	16820	50683;50684;50685	chr2:178568854;178568853;178568852	chr2:179433581;179433580;179433579
Novex-2	16887	50884;50885;50886	chr2:178568854;178568853;178568852	chr2:179433581;179433580;179433579
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-75
• Domain position: 63
• Structural Position: 96
• Q(SASA): 0.9486
• 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
N/K	None	None	0.892	N	0.496	0.232	0.126345400529	gnomAD-4.0.0	6.84495E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99604E-07	0	0
N/S	rs3813246	0.257	0.243	N	0.283	0.116	None	gnomAD-2.1.1	2.57166E-02	None	None	None	None	N	None	4.83791E-03	3.34768E-02	None	1.4612E-02	6.13756E-02	None	6.04891E-03	None	4.81879E-02	2.33044E-02	2.64565E-02
N/S	rs3813246	0.257	0.243	N	0.283	0.116	None	gnomAD-3.1.2	2.01989E-02	None	None	None	None	N	None	4.44166E-03	2.18619E-02	3.07018E-02	1.90202E-02	6.1339E-02	None	4.42036E-02	6.32911E-03	2.34033E-02	8.28157E-03	1.95985E-02
N/S	rs3813246	0.257	0.243	N	0.283	0.116	None	1000 genomes	2.23642E-02	None	None	None	None	N	None	8E-04	2.45E-02	None	None	6.05E-02	2.68E-02	None	None	None	6.1E-03	None
N/S	rs3813246	0.257	0.243	N	0.283	0.116	None	gnomAD-4.0.0	2.28761E-02	None	None	None	None	N	None	4.25367E-03	2.93706E-02	None	1.48719E-02	6.31891E-02	None	4.76071E-02	9.74884E-03	2.24335E-02	6.7762E-03	2.16459E-02

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
N/A	0.2207	likely_benign	0.2019	benign	-0.147	Destabilizing	0.845	D	0.48	neutral	None	None	None	None	N
N/C	0.4032	ambiguous	0.3643	ambiguous	0.242	Stabilizing	0.999	D	0.646	neutral	None	None	None	None	N
N/D	0.1319	likely_benign	0.1235	benign	0.123	Stabilizing	0.025	N	0.227	neutral	N	0.444213117	None	None	N
N/E	0.4348	ambiguous	0.3902	ambiguous	0.059	Stabilizing	0.845	D	0.476	neutral	None	None	None	None	N
N/F	0.6622	likely_pathogenic	0.6438	pathogenic	-0.738	Destabilizing	0.996	D	0.63	neutral	None	None	None	None	N
N/G	0.1901	likely_benign	0.1725	benign	-0.243	Destabilizing	0.916	D	0.48	neutral	None	None	None	None	N
N/H	0.1244	likely_benign	0.1124	benign	-0.279	Destabilizing	0.994	D	0.529	neutral	N	0.47261346	None	None	N
N/I	0.4866	ambiguous	0.4635	ambiguous	0.007	Stabilizing	0.983	D	0.626	neutral	N	0.51122828	None	None	N
N/K	0.3734	ambiguous	0.3406	ambiguous	0.17	Stabilizing	0.892	D	0.496	neutral	N	0.465225894	None	None	N
N/L	0.389	ambiguous	0.3653	ambiguous	0.007	Stabilizing	0.987	D	0.576	neutral	None	None	None	None	N
N/M	0.4906	ambiguous	0.4591	ambiguous	0.18	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
N/P	0.701	likely_pathogenic	0.674	pathogenic	-0.021	Destabilizing	0.987	D	0.576	neutral	None	None	None	None	N
N/Q	0.3667	ambiguous	0.3256	benign	-0.222	Destabilizing	0.987	D	0.517	neutral	None	None	None	None	N
N/R	0.4228	ambiguous	0.3848	ambiguous	0.237	Stabilizing	0.987	D	0.513	neutral	None	None	None	None	N
N/S	0.0789	likely_benign	0.077	benign	0.009	Stabilizing	0.243	N	0.283	neutral	N	0.487217319	None	None	N
N/T	0.1695	likely_benign	0.1578	benign	0.062	Stabilizing	0.805	D	0.482	neutral	N	0.474677375	None	None	N
N/V	0.4018	ambiguous	0.3774	ambiguous	-0.021	Destabilizing	0.987	D	0.616	neutral	None	None	None	None	N
N/W	0.86	likely_pathogenic	0.8396	pathogenic	-0.847	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
N/Y	0.2534	likely_benign	0.241	benign	-0.527	Destabilizing	0.994	D	0.576	neutral	N	0.499618485	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.