TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29519	88780;88781;88782	chr2:178554904;178554903;178554902	chr2:179419631;179419630;179419629
N2AB	27878	83857;83858;83859	chr2:178554904;178554903;178554902	chr2:179419631;179419630;179419629
N2A	26951	81076;81077;81078	chr2:178554904;178554903;178554902	chr2:179419631;179419630;179419629
N2B	20454	61585;61586;61587	chr2:178554904;178554903;178554902	chr2:179419631;179419630;179419629
Novex-1	20579	61960;61961;61962	chr2:178554904;178554903;178554902	chr2:179419631;179419630;179419629
Novex-2	20646	62161;62162;62163	chr2:178554904;178554903;178554902	chr2:179419631;179419630;179419629
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-146
• Domain position: 76
• Structural Position: 163
• Q(SASA): 0.5473
• 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
M/I	rs1559234546	None	None	N	0.248	0.137	0.40032279838	gnomAD-4.0.0	6.84201E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99433E-07	0	0
M/T	rs1019759612	None	0.024	N	0.483	0.292	0.556224665151	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
M/T	rs1019759612	None	0.024	N	0.483	0.292	0.556224665151	gnomAD-4.0.0	3.09832E-06	None	None	None	None	I	None	1.33426E-05	0	None	0	2.22926E-05	None	0	0	2.54269E-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
M/A	0.3697	ambiguous	0.3664	ambiguous	-0.137	Destabilizing	0.014	N	0.529	neutral	None	None	None	None	I
M/C	0.7115	likely_pathogenic	0.7037	pathogenic	-0.205	Destabilizing	0.628	D	0.515	neutral	None	None	None	None	I
M/D	0.9034	likely_pathogenic	0.9016	pathogenic	0.368	Stabilizing	0.628	D	0.554	neutral	None	None	None	None	I
M/E	0.6967	likely_pathogenic	0.6817	pathogenic	0.296	Stabilizing	0.136	N	0.556	neutral	None	None	None	None	I
M/F	0.3695	ambiguous	0.35	ambiguous	-0.173	Destabilizing	0.038	N	0.358	neutral	None	None	None	None	I
M/G	0.6624	likely_pathogenic	0.6642	pathogenic	-0.224	Destabilizing	0.136	N	0.543	neutral	None	None	None	None	I
M/H	0.5902	likely_pathogenic	0.5859	pathogenic	0.391	Stabilizing	0.628	D	0.567	neutral	None	None	None	None	I
M/I	0.4805	ambiguous	0.3974	ambiguous	-0.011	Destabilizing	None	N	0.248	neutral	N	0.44382162	None	None	I
M/K	0.3373	likely_benign	0.3222	benign	0.504	Stabilizing	0.106	N	0.473	neutral	N	0.478704984	None	None	I
M/L	0.129	likely_benign	0.1262	benign	-0.011	Destabilizing	None	N	0.242	neutral	N	0.356221278	None	None	I
M/N	0.6227	likely_pathogenic	0.6408	pathogenic	0.674	Stabilizing	0.628	D	0.568	neutral	None	None	None	None	I
M/P	0.9248	likely_pathogenic	0.9035	pathogenic	-0.029	Destabilizing	0.628	D	0.566	neutral	None	None	None	None	I
M/Q	0.3777	ambiguous	0.3683	ambiguous	0.503	Stabilizing	0.628	D	0.387	neutral	None	None	None	None	I
M/R	0.3255	likely_benign	0.2999	benign	0.926	Stabilizing	0.106	N	0.49	neutral	N	0.46793063	None	None	I
M/S	0.4464	ambiguous	0.4657	ambiguous	0.287	Stabilizing	0.136	N	0.481	neutral	None	None	None	None	I
M/T	0.2901	likely_benign	0.28	benign	0.301	Stabilizing	0.024	N	0.483	neutral	N	0.439626521	None	None	I
M/V	0.102	likely_benign	0.0933	benign	-0.029	Destabilizing	0.001	N	0.348	neutral	N	0.402935002	None	None	I
M/W	0.7144	likely_pathogenic	0.7042	pathogenic	-0.197	Destabilizing	0.864	D	0.526	neutral	None	None	None	None	I
M/Y	0.6158	likely_pathogenic	0.6148	pathogenic	0.021	Stabilizing	0.356	N	0.489	neutral	None	None	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.