TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24695	74308;74309;74310	chr2:178572049;178572048;178572047	chr2:179436776;179436775;179436774
N2AB	23054	69385;69386;69387	chr2:178572049;178572048;178572047	chr2:179436776;179436775;179436774
N2A	22127	66604;66605;66606	chr2:178572049;178572048;178572047	chr2:179436776;179436775;179436774
N2B	15630	47113;47114;47115	chr2:178572049;178572048;178572047	chr2:179436776;179436775;179436774
Novex-1	15755	47488;47489;47490	chr2:178572049;178572048;178572047	chr2:179436776;179436775;179436774
Novex-2	15822	47689;47690;47691	chr2:178572049;178572048;178572047	chr2:179436776;179436775;179436774
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: Fn3-67
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.1559
• 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/Q	None	None	0.934	N	0.687	0.27	0.254244900254	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6242	likely_pathogenic	0.6126	pathogenic	0.076	Stabilizing	0.781	D	0.591	neutral	None	None	None	None	N
K/C	0.7648	likely_pathogenic	0.778	pathogenic	-0.184	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
K/D	0.9547	likely_pathogenic	0.954	pathogenic	-0.05	Destabilizing	0.962	D	0.65	neutral	None	None	None	None	N
K/E	0.6716	likely_pathogenic	0.68	pathogenic	-0.054	Destabilizing	0.766	D	0.607	neutral	N	0.495988731	None	None	N
K/F	0.8972	likely_pathogenic	0.8894	pathogenic	-0.17	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
K/G	0.8359	likely_pathogenic	0.8409	pathogenic	-0.099	Destabilizing	0.022	N	0.458	neutral	None	None	None	None	N
K/H	0.5051	ambiguous	0.5223	ambiguous	-0.283	Destabilizing	0.996	D	0.692	prob.neutral	None	None	None	None	N
K/I	0.6654	likely_pathogenic	0.6405	pathogenic	0.453	Stabilizing	0.82	D	0.754	deleterious	None	None	None	None	N
K/L	0.7054	likely_pathogenic	0.6838	pathogenic	0.453	Stabilizing	0.599	D	0.65	neutral	None	None	None	None	N
K/M	0.4035	ambiguous	0.3836	ambiguous	0.178	Stabilizing	0.981	D	0.693	prob.neutral	N	0.468459177	None	None	N
K/N	0.7684	likely_pathogenic	0.7892	pathogenic	0.301	Stabilizing	0.95	D	0.667	neutral	N	0.4977596	None	None	N
K/P	0.9924	likely_pathogenic	0.9926	pathogenic	0.354	Stabilizing	0.994	D	0.686	prob.neutral	None	None	None	None	N
K/Q	0.3394	likely_benign	0.3432	ambiguous	0.116	Stabilizing	0.934	D	0.687	prob.neutral	N	0.507725877	None	None	N
K/R	0.1195	likely_benign	0.1176	benign	0.069	Stabilizing	0.669	D	0.575	neutral	N	0.467191729	None	None	N
K/S	0.8073	likely_pathogenic	0.8098	pathogenic	-0.141	Destabilizing	0.877	D	0.63	neutral	None	None	None	None	N
K/T	0.5768	likely_pathogenic	0.5411	ambiguous	-0.01	Destabilizing	0.92	D	0.649	neutral	N	0.516961436	None	None	N
K/V	0.574	likely_pathogenic	0.5505	ambiguous	0.354	Stabilizing	0.663	D	0.712	prob.delet.	None	None	None	None	N
K/W	0.9297	likely_pathogenic	0.9233	pathogenic	-0.213	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
K/Y	0.778	likely_pathogenic	0.7724	pathogenic	0.142	Stabilizing	0.878	D	0.758	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.