TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28604	86035;86036;86037	chr2:178560322;178560321;178560320	chr2:179425049;179425048;179425047
N2AB	26963	81112;81113;81114	chr2:178560322;178560321;178560320	chr2:179425049;179425048;179425047
N2A	26036	78331;78332;78333	chr2:178560322;178560321;178560320	chr2:179425049;179425048;179425047
N2B	19539	58840;58841;58842	chr2:178560322;178560321;178560320	chr2:179425049;179425048;179425047
Novex-1	19664	59215;59216;59217	chr2:178560322;178560321;178560320	chr2:179425049;179425048;179425047
Novex-2	19731	59416;59417;59418	chr2:178560322;178560321;178560320	chr2:179425049;179425048;179425047
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-96
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.4008
• 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
P/T	rs1208500218	-0.978	0.978	N	0.735	0.379	0.412328234245	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/T	rs1208500218	-0.978	0.978	N	0.735	0.379	0.412328234245	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31868E-05	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
P/A	0.0839	likely_benign	0.0863	benign	-0.827	Destabilizing	0.928	D	0.628	neutral	N	0.518902876	None	None	N
P/C	0.5002	ambiguous	0.5147	ambiguous	-0.638	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
P/D	0.681	likely_pathogenic	0.6854	pathogenic	-0.259	Destabilizing	0.997	D	0.822	deleterious	None	None	None	None	N
P/E	0.4521	ambiguous	0.4495	ambiguous	-0.318	Destabilizing	0.992	D	0.813	deleterious	None	None	None	None	N
P/F	0.541	ambiguous	0.56	ambiguous	-0.711	Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
P/G	0.4012	ambiguous	0.405	ambiguous	-1.053	Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
P/H	0.2857	likely_benign	0.2873	benign	-0.499	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
P/I	0.2507	likely_benign	0.2793	benign	-0.351	Destabilizing	0.968	D	0.805	deleterious	None	None	None	None	N
P/K	0.3955	ambiguous	0.3965	ambiguous	-0.604	Destabilizing	0.992	D	0.811	deleterious	None	None	None	None	N
P/L	0.0984	likely_benign	0.106	benign	-0.351	Destabilizing	0.085	N	0.518	neutral	N	0.456470338	None	None	N
P/M	0.2419	likely_benign	0.2636	benign	-0.386	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
P/N	0.4093	ambiguous	0.4249	ambiguous	-0.311	Destabilizing	0.997	D	0.837	deleterious	None	None	None	None	N
P/Q	0.234	likely_benign	0.2347	benign	-0.504	Destabilizing	0.996	D	0.834	deleterious	N	0.475914688	None	None	N
P/R	0.2603	likely_benign	0.2596	benign	-0.108	Destabilizing	0.989	D	0.837	deleterious	N	0.478824336	None	None	N
P/S	0.1931	likely_benign	0.198	benign	-0.804	Destabilizing	0.989	D	0.788	deleterious	N	0.487830608	None	None	N
P/T	0.1086	likely_benign	0.1143	benign	-0.751	Destabilizing	0.978	D	0.735	prob.delet.	N	0.471613149	None	None	N
P/V	0.1613	likely_benign	0.1812	benign	-0.473	Destabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	N
P/W	0.646	likely_pathogenic	0.6471	pathogenic	-0.801	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
P/Y	0.4785	ambiguous	0.4937	ambiguous	-0.517	Destabilizing	0.998	D	0.833	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.