TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4936	15031;15032;15033	chr2:178735640;178735639;178735638	chr2:179600367;179600366;179600365
N2AB	4619	14080;14081;14082	chr2:178735640;178735639;178735638	chr2:179600367;179600366;179600365
N2A	3692	11299;11300;11301	chr2:178735640;178735639;178735638	chr2:179600367;179600366;179600365
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-32
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2102
• 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
I/M	None	None	0.019	N	0.282	0.175	0.551009825273	gnomAD-4.0.0	6.8426E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99467E-07	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
I/A	0.4342	ambiguous	0.4814	ambiguous	-2.073	Highly Destabilizing	0.055	N	0.402	neutral	None	None	None	None	N
I/C	0.6749	likely_pathogenic	0.7184	pathogenic	-1.28	Destabilizing	0.958	D	0.578	neutral	None	None	None	None	N
I/D	0.7762	likely_pathogenic	0.8181	pathogenic	-1.55	Destabilizing	0.859	D	0.65	neutral	None	None	None	None	N
I/E	0.6682	likely_pathogenic	0.7211	pathogenic	-1.444	Destabilizing	0.667	D	0.657	neutral	None	None	None	None	N
I/F	0.1137	likely_benign	0.1296	benign	-1.326	Destabilizing	0.001	N	0.275	neutral	N	0.516937466	None	None	N
I/G	0.6847	likely_pathogenic	0.7316	pathogenic	-2.511	Highly Destabilizing	0.364	N	0.661	neutral	None	None	None	None	N
I/H	0.5475	ambiguous	0.5896	pathogenic	-1.751	Destabilizing	0.958	D	0.633	neutral	None	None	None	None	N
I/K	0.5161	ambiguous	0.5773	pathogenic	-1.439	Destabilizing	0.497	N	0.659	neutral	None	None	None	None	N
I/L	0.1085	likely_benign	0.1167	benign	-0.879	Destabilizing	None	N	0.115	neutral	N	0.505880353	None	None	N
I/M	0.0887	likely_benign	0.0983	benign	-0.701	Destabilizing	0.019	N	0.282	neutral	N	0.507406558	None	None	N
I/N	0.3304	likely_benign	0.36	ambiguous	-1.413	Destabilizing	0.602	D	0.645	neutral	D	0.655809071	None	None	N
I/P	0.7635	likely_pathogenic	0.7989	pathogenic	-1.25	Destabilizing	0.859	D	0.645	neutral	None	None	None	None	N
I/Q	0.5143	ambiguous	0.57	pathogenic	-1.443	Destabilizing	0.667	D	0.643	neutral	None	None	None	None	N
I/R	0.4048	ambiguous	0.4579	ambiguous	-0.995	Destabilizing	0.667	D	0.644	neutral	None	None	None	None	N
I/S	0.3672	ambiguous	0.4043	ambiguous	-2.127	Highly Destabilizing	0.175	N	0.588	neutral	D	0.573662045	None	None	N
I/T	0.3381	likely_benign	0.3628	ambiguous	-1.882	Destabilizing	0.175	N	0.517	neutral	D	0.556207529	None	None	N
I/V	0.1063	likely_benign	0.1138	benign	-1.25	Destabilizing	None	N	0.147	neutral	N	0.502413536	None	None	N
I/W	0.6766	likely_pathogenic	0.7276	pathogenic	-1.507	Destabilizing	0.958	D	0.645	neutral	None	None	None	None	N
I/Y	0.3595	ambiguous	0.3939	ambiguous	-1.252	Destabilizing	0.331	N	0.611	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.