TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33522	100789;100790;100791	chr2:178536183;178536182;178536181	chr2:179400910;179400909;179400908
N2AB	31881	95866;95867;95868	chr2:178536183;178536182;178536181	chr2:179400910;179400909;179400908
N2A	30954	93085;93086;93087	chr2:178536183;178536182;178536181	chr2:179400910;179400909;179400908
N2B	24457	73594;73595;73596	chr2:178536183;178536182;178536181	chr2:179400910;179400909;179400908
Novex-1	24582	73969;73970;73971	chr2:178536183;178536182;178536181	chr2:179400910;179400909;179400908
Novex-2	24649	74170;74171;74172	chr2:178536183;178536182;178536181	chr2:179400910;179400909;179400908
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-158
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5569
• Predicted PPI site: I

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
H/D	None	None	0.468	N	0.481	0.304	0.311079019809	gnomAD-4.0.0	1.59207E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85953E-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
H/A	0.518	ambiguous	0.4985	ambiguous	0.39	Stabilizing	0.886	D	0.519	neutral	None	None	None	None	I
H/C	0.2502	likely_benign	0.2608	benign	0.478	Stabilizing	0.995	D	0.525	neutral	None	None	None	None	I
H/D	0.5424	ambiguous	0.5834	pathogenic	-0.297	Destabilizing	0.468	N	0.481	neutral	N	0.432700549	None	None	I
H/E	0.5286	ambiguous	0.5364	ambiguous	-0.302	Destabilizing	0.617	D	0.359	neutral	None	None	None	None	I
H/F	0.2454	likely_benign	0.2138	benign	0.801	Stabilizing	0.883	D	0.495	neutral	None	None	None	None	I
H/G	0.7394	likely_pathogenic	0.7322	pathogenic	0.2	Stabilizing	0.886	D	0.542	neutral	None	None	None	None	I
H/I	0.3075	likely_benign	0.2998	benign	0.849	Stabilizing	0.956	D	0.523	neutral	None	None	None	None	I
H/K	0.44	ambiguous	0.4313	ambiguous	0.288	Stabilizing	0.607	D	0.493	neutral	None	None	None	None	I
H/L	0.1833	likely_benign	0.1845	benign	0.849	Stabilizing	0.699	D	0.558	neutral	N	0.479705062	None	None	I
H/M	0.5039	ambiguous	0.4805	ambiguous	0.528	Stabilizing	0.996	D	0.529	neutral	None	None	None	None	I
H/N	0.1563	likely_benign	0.1576	benign	0.156	Stabilizing	0.023	N	0.271	neutral	N	0.443378902	None	None	I
H/P	0.8533	likely_pathogenic	0.8532	pathogenic	0.718	Stabilizing	0.974	D	0.542	neutral	N	0.48742753	None	None	I
H/Q	0.2522	likely_benign	0.247	benign	0.194	Stabilizing	0.179	N	0.236	neutral	N	0.455846767	None	None	I
H/R	0.2407	likely_benign	0.2446	benign	-0.125	Destabilizing	0.699	D	0.411	neutral	N	0.47585668	None	None	I
H/S	0.3433	ambiguous	0.3251	benign	0.287	Stabilizing	0.886	D	0.489	neutral	None	None	None	None	I
H/T	0.3732	ambiguous	0.3811	ambiguous	0.366	Stabilizing	0.699	D	0.553	neutral	None	None	None	None	I
H/V	0.3044	likely_benign	0.2912	benign	0.718	Stabilizing	0.867	D	0.519	neutral	None	None	None	None	I
H/W	0.4647	ambiguous	0.4546	ambiguous	0.654	Stabilizing	0.999	D	0.543	neutral	None	None	None	None	I
H/Y	0.0834	likely_benign	0.0797	benign	0.924	Stabilizing	0.042	N	0.271	neutral	N	0.455270764	None	None	I

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.