TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15528	46807;46808;46809	chr2:178619735;178619734;178619733	chr2:179484462;179484461;179484460
N2AB	13887	41884;41885;41886	chr2:178619735;178619734;178619733	chr2:179484462;179484461;179484460
N2A	12960	39103;39104;39105	chr2:178619735;178619734;178619733	chr2:179484462;179484461;179484460
N2B	6463	19612;19613;19614	chr2:178619735;178619734;178619733	chr2:179484462;179484461;179484460
Novex-1	6588	19987;19988;19989	chr2:178619735;178619734;178619733	chr2:179484462;179484461;179484460
Novex-2	6655	20188;20189;20190	chr2:178619735;178619734;178619733	chr2:179484462;179484461;179484460
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-107
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.3213
• 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
M/L	None	None	0.03	N	0.087	0.217	0.506189230309	gnomAD-4.0.0	3.18777E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72793E-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	0.513	ambiguous	0.5892	pathogenic	-0.499	Destabilizing	0.927	D	0.303	neutral	None	None	None	None	N
M/C	0.7838	likely_pathogenic	0.8332	pathogenic	-0.51	Destabilizing	1.0	D	0.386	neutral	None	None	None	None	N
M/D	0.8824	likely_pathogenic	0.9033	pathogenic	0.27	Stabilizing	0.999	D	0.473	neutral	None	None	None	None	N
M/E	0.6129	likely_pathogenic	0.6647	pathogenic	0.216	Stabilizing	0.999	D	0.423	neutral	None	None	None	None	N
M/F	0.3062	likely_benign	0.3188	benign	-0.133	Destabilizing	0.969	D	0.345	neutral	None	None	None	None	N
M/G	0.7535	likely_pathogenic	0.812	pathogenic	-0.683	Destabilizing	0.995	D	0.415	neutral	None	None	None	None	N
M/H	0.5771	likely_pathogenic	0.6145	pathogenic	0.124	Stabilizing	1.0	D	0.44	neutral	None	None	None	None	N
M/I	0.2954	likely_benign	0.313	benign	-0.109	Destabilizing	0.828	D	0.278	neutral	N	0.43302736	None	None	N
M/K	0.3359	likely_benign	0.3976	ambiguous	0.393	Stabilizing	0.993	D	0.346	neutral	N	0.445855464	None	None	N
M/L	0.1596	likely_benign	0.1736	benign	-0.109	Destabilizing	0.03	N	0.087	neutral	N	0.464505007	None	None	N
M/N	0.5561	ambiguous	0.6111	pathogenic	0.542	Stabilizing	0.999	D	0.458	neutral	None	None	None	None	N
M/P	0.9828	likely_pathogenic	0.9854	pathogenic	-0.21	Destabilizing	0.999	D	0.452	neutral	None	None	None	None	N
M/Q	0.3122	likely_benign	0.3391	benign	0.36	Stabilizing	0.999	D	0.363	neutral	None	None	None	None	N
M/R	0.3597	ambiguous	0.4035	ambiguous	0.885	Stabilizing	0.998	D	0.387	neutral	N	0.454445568	None	None	N
M/S	0.5089	ambiguous	0.5698	pathogenic	0.071	Stabilizing	0.984	D	0.295	neutral	None	None	None	None	N
M/T	0.3438	ambiguous	0.3858	ambiguous	0.119	Stabilizing	0.959	D	0.307	neutral	N	0.397177489	None	None	N
M/V	0.1096	likely_benign	0.1225	benign	-0.21	Destabilizing	0.116	N	0.085	neutral	N	0.441423793	None	None	N
M/W	0.7014	likely_pathogenic	0.74	pathogenic	-0.098	Destabilizing	1.0	D	0.409	neutral	None	None	None	None	N
M/Y	0.6012	likely_pathogenic	0.6438	pathogenic	0.051	Stabilizing	0.999	D	0.395	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.