TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29542	88849;88850;88851	chr2:178554723;178554722;178554721	chr2:179419450;179419449;179419448
N2AB	27901	83926;83927;83928	chr2:178554723;178554722;178554721	chr2:179419450;179419449;179419448
N2A	26974	81145;81146;81147	chr2:178554723;178554722;178554721	chr2:179419450;179419449;179419448
N2B	20477	61654;61655;61656	chr2:178554723;178554722;178554721	chr2:179419450;179419449;179419448
Novex-1	20602	62029;62030;62031	chr2:178554723;178554722;178554721	chr2:179419450;179419449;179419448
Novex-2	20669	62230;62231;62232	chr2:178554723;178554722;178554721	chr2:179419450;179419449;179419448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-103
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.3584
• 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
E/K	None	None	0.454	N	0.485	0.173	0.231231049324	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
E/A	0.127	likely_benign	0.142	benign	-0.515	Destabilizing	0.625	D	0.451	neutral	N	0.50774452	None	None	N
E/C	0.7212	likely_pathogenic	0.7249	pathogenic	-0.364	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
E/D	0.1462	likely_benign	0.1591	benign	-0.651	Destabilizing	0.625	D	0.432	neutral	N	0.489332118	None	None	N
E/F	0.6268	likely_pathogenic	0.662	pathogenic	0.201	Stabilizing	0.991	D	0.646	neutral	None	None	None	None	N
E/G	0.2337	likely_benign	0.2642	benign	-0.842	Destabilizing	0.801	D	0.56	neutral	N	0.472204932	None	None	N
E/H	0.3462	ambiguous	0.3582	ambiguous	0.262	Stabilizing	0.974	D	0.531	neutral	None	None	None	None	N
E/I	0.2076	likely_benign	0.2255	benign	0.362	Stabilizing	0.974	D	0.654	neutral	None	None	None	None	N
E/K	0.177	likely_benign	0.191	benign	-0.025	Destabilizing	0.454	N	0.485	neutral	N	0.446770632	None	None	N
E/L	0.2775	likely_benign	0.3015	benign	0.362	Stabilizing	0.842	D	0.592	neutral	None	None	None	None	N
E/M	0.333	likely_benign	0.363	ambiguous	0.448	Stabilizing	0.974	D	0.636	neutral	None	None	None	None	N
E/N	0.2335	likely_benign	0.2478	benign	-0.699	Destabilizing	0.842	D	0.48	neutral	None	None	None	None	N
E/P	0.864	likely_pathogenic	0.8783	pathogenic	0.091	Stabilizing	0.974	D	0.583	neutral	None	None	None	None	N
E/Q	0.1081	likely_benign	0.1144	benign	-0.548	Destabilizing	0.007	N	0.183	neutral	N	0.462894878	None	None	N
E/R	0.2604	likely_benign	0.2772	benign	0.332	Stabilizing	0.728	D	0.456	neutral	None	None	None	None	N
E/S	0.17	likely_benign	0.1827	benign	-0.899	Destabilizing	0.688	D	0.451	neutral	None	None	None	None	N
E/T	0.1474	likely_benign	0.1586	benign	-0.611	Destabilizing	0.842	D	0.489	neutral	None	None	None	None	N
E/V	0.1357	likely_benign	0.1504	benign	0.091	Stabilizing	0.891	D	0.591	neutral	N	0.488177324	None	None	N
E/W	0.8708	likely_pathogenic	0.8918	pathogenic	0.51	Stabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
E/Y	0.5003	ambiguous	0.5367	ambiguous	0.484	Stabilizing	0.991	D	0.65	neutral	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.