TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5198	15817;15818;15819	chr2:178733797;178733796;178733795	chr2:179598524;179598523;179598522
N2AB	4881	14866;14867;14868	chr2:178733797;178733796;178733795	chr2:179598524;179598523;179598522
N2A	3954	12085;12086;12087	chr2:178733797;178733796;178733795	chr2:179598524;179598523;179598522
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-35
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.3595
• 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
S/F	None	None	None	D	0.365	0.339	0.532359089423	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0733	likely_benign	0.0793	benign	-0.424	Destabilizing	0.012	N	0.352	neutral	N	0.508890129	None	None	N
S/C	0.1364	likely_benign	0.1452	benign	-0.454	Destabilizing	0.828	D	0.489	neutral	D	0.730447578	None	None	N
S/D	0.3243	likely_benign	0.3887	ambiguous	0.445	Stabilizing	0.038	N	0.399	neutral	None	None	None	None	N
S/E	0.3991	ambiguous	0.462	ambiguous	0.418	Stabilizing	0.072	N	0.397	neutral	None	None	None	None	N
S/F	0.1314	likely_benign	0.1358	benign	-0.878	Destabilizing	None	N	0.365	neutral	D	0.66974892	None	None	N
S/G	0.1215	likely_benign	0.143	benign	-0.599	Destabilizing	0.031	N	0.411	neutral	None	None	None	None	N
S/H	0.2401	likely_benign	0.2662	benign	-0.901	Destabilizing	0.214	N	0.53	neutral	None	None	None	None	N
S/I	0.1376	likely_benign	0.1657	benign	-0.08	Destabilizing	0.038	N	0.579	neutral	None	None	None	None	N
S/K	0.4234	ambiguous	0.5106	ambiguous	-0.292	Destabilizing	0.072	N	0.399	neutral	None	None	None	None	N
S/L	0.085	likely_benign	0.0902	benign	-0.08	Destabilizing	0.016	N	0.484	neutral	None	None	None	None	N
S/M	0.1625	likely_benign	0.1833	benign	-0.189	Destabilizing	0.356	N	0.517	neutral	None	None	None	None	N
S/N	0.1282	likely_benign	0.1546	benign	-0.26	Destabilizing	0.001	N	0.163	neutral	None	None	None	None	N
S/P	0.7616	likely_pathogenic	0.8099	pathogenic	-0.163	Destabilizing	0.295	N	0.56	neutral	D	0.653146146	None	None	N
S/Q	0.3636	ambiguous	0.422	ambiguous	-0.34	Destabilizing	0.356	N	0.497	neutral	None	None	None	None	N
S/R	0.3455	ambiguous	0.4067	ambiguous	-0.179	Destabilizing	0.214	N	0.557	neutral	None	None	None	None	N
S/T	0.0604	likely_benign	0.067	benign	-0.32	Destabilizing	None	N	0.109	neutral	N	0.456241479	None	None	N
S/V	0.1366	likely_benign	0.1559	benign	-0.163	Destabilizing	0.038	N	0.519	neutral	None	None	None	None	N
S/W	0.2903	likely_benign	0.2957	benign	-0.919	Destabilizing	0.676	D	0.584	neutral	None	None	None	None	N
S/Y	0.1343	likely_benign	0.1295	benign	-0.59	Destabilizing	None	N	0.369	neutral	D	0.640635761	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.