TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18957	57094;57095;57096	chr2:178598841;178598840;178598839	chr2:179463568;179463567;179463566
N2AB	17316	52171;52172;52173	chr2:178598841;178598840;178598839	chr2:179463568;179463567;179463566
N2A	16389	49390;49391;49392	chr2:178598841;178598840;178598839	chr2:179463568;179463567;179463566
N2B	9892	29899;29900;29901	chr2:178598841;178598840;178598839	chr2:179463568;179463567;179463566
Novex-1	10017	30274;30275;30276	chr2:178598841;178598840;178598839	chr2:179463568;179463567;179463566
Novex-2	10084	30475;30476;30477	chr2:178598841;178598840;178598839	chr2:179463568;179463567;179463566
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-25
• Domain position: 74
• Structural Position: 102
• Q(SASA): 0.2082
• 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	0.188	N	0.437	0.276	0.518367700685	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-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
S/A	0.0971	likely_benign	0.0985	benign	-0.878	Destabilizing	0.001	N	0.084	neutral	N	0.432785402	None	None	N
S/C	0.1105	likely_benign	0.1013	benign	-0.655	Destabilizing	0.78	D	0.375	neutral	N	0.497722314	None	None	N
S/D	0.809	likely_pathogenic	0.7923	pathogenic	-0.814	Destabilizing	0.149	N	0.385	neutral	None	None	None	None	N
S/E	0.8246	likely_pathogenic	0.8057	pathogenic	-0.773	Destabilizing	0.149	N	0.331	neutral	None	None	None	None	N
S/F	0.4235	ambiguous	0.4237	ambiguous	-1.031	Destabilizing	0.188	N	0.437	neutral	N	0.481385645	None	None	N
S/G	0.145	likely_benign	0.1488	benign	-1.164	Destabilizing	0.035	N	0.293	neutral	None	None	None	None	N
S/H	0.5781	likely_pathogenic	0.5317	ambiguous	-1.65	Destabilizing	0.38	N	0.379	neutral	None	None	None	None	N
S/I	0.3492	ambiguous	0.3101	benign	-0.21	Destabilizing	0.081	N	0.427	neutral	None	None	None	None	N
S/K	0.9094	likely_pathogenic	0.8847	pathogenic	-0.773	Destabilizing	0.149	N	0.329	neutral	None	None	None	None	N
S/L	0.1611	likely_benign	0.1636	benign	-0.21	Destabilizing	0.081	N	0.343	neutral	None	None	None	None	N
S/M	0.2452	likely_benign	0.2409	benign	0.102	Stabilizing	0.555	D	0.377	neutral	None	None	None	None	N
S/N	0.2473	likely_benign	0.2258	benign	-0.953	Destabilizing	0.149	N	0.417	neutral	None	None	None	None	N
S/P	0.9766	likely_pathogenic	0.9674	pathogenic	-0.398	Destabilizing	0.484	N	0.383	neutral	N	0.492653045	None	None	N
S/Q	0.6925	likely_pathogenic	0.6566	pathogenic	-1.051	Destabilizing	0.555	D	0.384	neutral	None	None	None	None	N
S/R	0.8616	likely_pathogenic	0.8315	pathogenic	-0.717	Destabilizing	0.38	N	0.398	neutral	None	None	None	None	N
S/T	0.1243	likely_benign	0.1166	benign	-0.867	Destabilizing	None	N	0.137	neutral	N	0.419983889	None	None	N
S/V	0.3041	likely_benign	0.2738	benign	-0.398	Destabilizing	0.081	N	0.33	neutral	None	None	None	None	N
S/W	0.6213	likely_pathogenic	0.6043	pathogenic	-1.054	Destabilizing	0.824	D	0.465	neutral	None	None	None	None	N
S/Y	0.3712	ambiguous	0.3408	ambiguous	-0.754	Destabilizing	None	N	0.255	neutral	N	0.481132155	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.