TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32613	98062;98063;98064	chr2:178540329;178540328;178540327	chr2:179405056;179405055;179405054
N2AB	30972	93139;93140;93141	chr2:178540329;178540328;178540327	chr2:179405056;179405055;179405054
N2A	30045	90358;90359;90360	chr2:178540329;178540328;178540327	chr2:179405056;179405055;179405054
N2B	23548	70867;70868;70869	chr2:178540329;178540328;178540327	chr2:179405056;179405055;179405054
Novex-1	23673	71242;71243;71244	chr2:178540329;178540328;178540327	chr2:179405056;179405055;179405054
Novex-2	23740	71443;71444;71445	chr2:178540329;178540328;178540327	chr2:179405056;179405055;179405054
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-126
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2223
• 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
T/K	None	None	1.0	N	0.791	0.448	0.635465298753	gnomAD-4.0.0	6.00175E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56268E-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
T/A	0.444	ambiguous	0.42	ambiguous	-0.563	Destabilizing	0.999	D	0.481	neutral	N	0.489440722	None	None	N
T/C	0.8757	likely_pathogenic	0.8604	pathogenic	-0.37	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
T/D	0.857	likely_pathogenic	0.836	pathogenic	-0.821	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
T/E	0.9277	likely_pathogenic	0.9093	pathogenic	-0.866	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/F	0.9362	likely_pathogenic	0.9191	pathogenic	-1.044	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/G	0.5087	ambiguous	0.4876	ambiguous	-0.735	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
T/H	0.8396	likely_pathogenic	0.8142	pathogenic	-1.202	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/I	0.9596	likely_pathogenic	0.9462	pathogenic	-0.211	Destabilizing	1.0	D	0.783	deleterious	N	0.513585364	None	None	N
T/K	0.8529	likely_pathogenic	0.8156	pathogenic	-0.54	Destabilizing	1.0	D	0.791	deleterious	N	0.487376807	None	None	N
T/L	0.6591	likely_pathogenic	0.622	pathogenic	-0.211	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
T/M	0.5401	ambiguous	0.5136	ambiguous	0.33	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/N	0.511	ambiguous	0.4599	ambiguous	-0.521	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/P	0.9262	likely_pathogenic	0.9202	pathogenic	-0.3	Destabilizing	1.0	D	0.764	deleterious	N	0.518358304	None	None	N
T/Q	0.8192	likely_pathogenic	0.7831	pathogenic	-0.881	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/R	0.8329	likely_pathogenic	0.7939	pathogenic	-0.197	Destabilizing	1.0	D	0.767	deleterious	N	0.473703097	None	None	N
T/S	0.2048	likely_benign	0.2033	benign	-0.644	Destabilizing	0.999	D	0.512	neutral	N	0.444407905	None	None	N
T/V	0.8498	likely_pathogenic	0.8196	pathogenic	-0.3	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
T/W	0.9822	likely_pathogenic	0.9794	pathogenic	-1.011	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/Y	0.9279	likely_pathogenic	0.9112	pathogenic	-0.706	Destabilizing	1.0	D	0.779	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.