TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26874	80845;80846;80847	chr2:178565512;178565511;178565510	chr2:179430239;179430238;179430237
N2AB	25233	75922;75923;75924	chr2:178565512;178565511;178565510	chr2:179430239;179430238;179430237
N2A	24306	73141;73142;73143	chr2:178565512;178565511;178565510	chr2:179430239;179430238;179430237
N2B	17809	53650;53651;53652	chr2:178565512;178565511;178565510	chr2:179430239;179430238;179430237
Novex-1	17934	54025;54026;54027	chr2:178565512;178565511;178565510	chr2:179430239;179430238;179430237
Novex-2	18001	54226;54227;54228	chr2:178565512;178565511;178565510	chr2:179430239;179430238;179430237
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-83
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.5673
• 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/E	rs372155974	0.337	0.059	D	0.506	0.231	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/E	rs372155974	0.337	0.059	D	0.506	0.231	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs372155974	0.337	0.059	D	0.506	0.231	None	gnomAD-4.0.0	6.57531E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47089E-05	0	0
K/T	None	None	0.059	N	0.661	0.259	0.319970858106	gnomAD-4.0.0	2.7373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59835E-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	0.5954	likely_pathogenic	0.5443	ambiguous	-0.386	Destabilizing	0.218	N	0.611	neutral	None	None	None	None	N
K/C	0.8281	likely_pathogenic	0.8103	pathogenic	-0.481	Destabilizing	0.978	D	0.859	deleterious	None	None	None	None	N
K/D	0.8622	likely_pathogenic	0.8375	pathogenic	0.074	Stabilizing	0.218	N	0.677	prob.neutral	None	None	None	None	N
K/E	0.3554	ambiguous	0.3299	benign	0.131	Stabilizing	0.059	N	0.506	neutral	D	0.523375694	None	None	N
K/F	0.9419	likely_pathogenic	0.9396	pathogenic	-0.343	Destabilizing	0.612	D	0.792	deleterious	None	None	None	None	N
K/G	0.7107	likely_pathogenic	0.6655	pathogenic	-0.682	Destabilizing	0.218	N	0.607	neutral	None	None	None	None	N
K/H	0.4715	ambiguous	0.4647	ambiguous	-1.048	Destabilizing	0.448	N	0.574	neutral	None	None	None	None	N
K/I	0.7019	likely_pathogenic	0.6748	pathogenic	0.342	Stabilizing	0.104	N	0.808	deleterious	None	None	None	None	N
K/L	0.6926	likely_pathogenic	0.6628	pathogenic	0.342	Stabilizing	0.016	N	0.637	neutral	None	None	None	None	N
K/M	0.4731	ambiguous	0.4484	ambiguous	0.257	Stabilizing	0.804	D	0.581	neutral	N	0.49797046	None	None	N
K/N	0.6932	likely_pathogenic	0.6187	pathogenic	-0.174	Destabilizing	0.001	N	0.317	neutral	N	0.491587678	None	None	N
K/P	0.9774	likely_pathogenic	0.9762	pathogenic	0.13	Stabilizing	0.798	D	0.627	neutral	None	None	None	None	N
K/Q	0.1928	likely_benign	0.1897	benign	-0.342	Destabilizing	0.151	N	0.535	neutral	N	0.483016076	None	None	N
K/R	0.0886	likely_benign	0.0848	benign	-0.395	Destabilizing	0.001	N	0.286	neutral	N	0.485318738	None	None	N
K/S	0.6448	likely_pathogenic	0.5833	pathogenic	-0.822	Destabilizing	0.007	N	0.325	neutral	None	None	None	None	N
K/T	0.3489	ambiguous	0.3125	benign	-0.58	Destabilizing	0.059	N	0.661	prob.neutral	N	0.502690494	None	None	N
K/V	0.5771	likely_pathogenic	0.5429	ambiguous	0.13	Stabilizing	0.07	N	0.655	prob.neutral	None	None	None	None	N
K/W	0.9126	likely_pathogenic	0.9124	pathogenic	-0.224	Destabilizing	0.985	D	0.87	deleterious	None	None	None	None	N
K/Y	0.858	likely_pathogenic	0.8493	pathogenic	0.088	Stabilizing	0.156	N	0.808	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.