TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27810	83653;83654;83655	chr2:178562704;178562703;178562702	chr2:179427431;179427430;179427429
N2AB	26169	78730;78731;78732	chr2:178562704;178562703;178562702	chr2:179427431;179427430;179427429
N2A	25242	75949;75950;75951	chr2:178562704;178562703;178562702	chr2:179427431;179427430;179427429
N2B	18745	56458;56459;56460	chr2:178562704;178562703;178562702	chr2:179427431;179427430;179427429
Novex-1	18870	56833;56834;56835	chr2:178562704;178562703;178562702	chr2:179427431;179427430;179427429
Novex-2	18937	57034;57035;57036	chr2:178562704;178562703;178562702	chr2:179427431;179427430;179427429
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-90
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.352
• 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
R/T	None	None	0.961	N	0.369	0.369	0.344483371355	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
R/A	0.9643	likely_pathogenic	0.9816	pathogenic	-0.444	Destabilizing	0.903	D	0.407	neutral	None	None	None	None	N
R/C	0.7021	likely_pathogenic	0.8503	pathogenic	-0.378	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
R/D	0.9939	likely_pathogenic	0.9965	pathogenic	0.025	Stabilizing	0.97	D	0.375	neutral	None	None	None	None	N
R/E	0.9561	likely_pathogenic	0.9771	pathogenic	0.109	Stabilizing	0.583	D	0.366	neutral	None	None	None	None	N
R/F	0.9759	likely_pathogenic	0.9851	pathogenic	-0.5	Destabilizing	0.988	D	0.522	neutral	None	None	None	None	N
R/G	0.8936	likely_pathogenic	0.9377	pathogenic	-0.697	Destabilizing	0.875	D	0.333	neutral	N	0.504874786	None	None	N
R/H	0.5053	ambiguous	0.643	pathogenic	-1.095	Destabilizing	0.965	D	0.337	neutral	None	None	None	None	N
R/I	0.9603	likely_pathogenic	0.979	pathogenic	0.21	Stabilizing	0.954	D	0.528	neutral	N	0.492777949	None	None	N
R/K	0.3821	ambiguous	0.494	ambiguous	-0.444	Destabilizing	0.148	N	0.409	neutral	N	0.489849406	None	None	N
R/L	0.8705	likely_pathogenic	0.9251	pathogenic	0.21	Stabilizing	0.794	D	0.333	neutral	None	None	None	None	N
R/M	0.9114	likely_pathogenic	0.9573	pathogenic	-0.08	Destabilizing	0.99	D	0.365	neutral	None	None	None	None	N
R/N	0.9853	likely_pathogenic	0.9916	pathogenic	0.065	Stabilizing	0.97	D	0.319	neutral	None	None	None	None	N
R/P	0.9942	likely_pathogenic	0.9961	pathogenic	0.013	Stabilizing	0.985	D	0.439	neutral	None	None	None	None	N
R/Q	0.451	ambiguous	0.6196	pathogenic	-0.137	Destabilizing	0.175	N	0.308	neutral	None	None	None	None	N
R/S	0.9791	likely_pathogenic	0.9889	pathogenic	-0.562	Destabilizing	0.875	D	0.371	neutral	N	0.481883283	None	None	N
R/T	0.9663	likely_pathogenic	0.9843	pathogenic	-0.32	Destabilizing	0.961	D	0.369	neutral	N	0.506992372	None	None	N
R/V	0.9636	likely_pathogenic	0.9804	pathogenic	0.013	Stabilizing	0.907	D	0.522	neutral	None	None	None	None	N
R/W	0.6957	likely_pathogenic	0.814	pathogenic	-0.316	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
R/Y	0.9187	likely_pathogenic	0.9513	pathogenic	0.029	Stabilizing	0.988	D	0.437	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.