TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17417	52474;52475;52476	chr2:178608762;178608761;178608760	chr2:179473489;179473488;179473487
N2AB	15776	47551;47552;47553	chr2:178608762;178608761;178608760	chr2:179473489;179473488;179473487
N2A	14849	44770;44771;44772	chr2:178608762;178608761;178608760	chr2:179473489;179473488;179473487
N2B	8352	25279;25280;25281	chr2:178608762;178608761;178608760	chr2:179473489;179473488;179473487
Novex-1	8477	25654;25655;25656	chr2:178608762;178608761;178608760	chr2:179473489;179473488;179473487
Novex-2	8544	25855;25856;25857	chr2:178608762;178608761;178608760	chr2:179473489;179473488;179473487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-14
• Domain position: 49
• Structural Position: 64
• Q(SASA): 0.3415
• 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
E/G	rs1316644497	-1.401	None	N	0.209	0.132	0.238096912614	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs1316644497	-1.401	None	N	0.209	0.132	0.238096912614	gnomAD-4.0.0	1.59375E-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
E/A	0.1725	likely_benign	0.1652	benign	-0.241	Destabilizing	0.012	N	0.309	neutral	N	0.475517458	None	None	N
E/C	0.8033	likely_pathogenic	0.7527	pathogenic	-0.327	Destabilizing	0.864	D	0.323	neutral	None	None	None	None	N
E/D	0.0752	likely_benign	0.0731	benign	-0.24	Destabilizing	None	N	0.111	neutral	N	0.470458355	None	None	N
E/F	0.8264	likely_pathogenic	0.7582	pathogenic	-0.086	Destabilizing	0.628	D	0.327	neutral	None	None	None	None	N
E/G	0.1551	likely_benign	0.1499	benign	-0.404	Destabilizing	None	N	0.209	neutral	N	0.405446872	None	None	N
E/H	0.4986	ambiguous	0.4395	ambiguous	0.47	Stabilizing	0.356	N	0.233	neutral	None	None	None	None	N
E/I	0.4581	ambiguous	0.4036	ambiguous	0.148	Stabilizing	0.356	N	0.341	neutral	None	None	None	None	N
E/K	0.2446	likely_benign	0.207	benign	0.235	Stabilizing	0.055	N	0.213	neutral	N	0.465263179	None	None	N
E/L	0.4661	ambiguous	0.4231	ambiguous	0.148	Stabilizing	0.072	N	0.305	neutral	None	None	None	None	N
E/M	0.591	likely_pathogenic	0.5371	ambiguous	-0.045	Destabilizing	0.864	D	0.299	neutral	None	None	None	None	N
E/N	0.2013	likely_benign	0.1791	benign	-0.086	Destabilizing	0.038	N	0.191	neutral	None	None	None	None	N
E/P	0.2945	likely_benign	0.2841	benign	0.037	Stabilizing	0.136	N	0.273	neutral	None	None	None	None	N
E/Q	0.1874	likely_benign	0.1701	benign	-0.039	Destabilizing	0.055	N	0.253	neutral	N	0.465783254	None	None	N
E/R	0.3965	ambiguous	0.3297	benign	0.572	Stabilizing	0.072	N	0.239	neutral	None	None	None	None	N
E/S	0.1755	likely_benign	0.1614	benign	-0.256	Destabilizing	0.016	N	0.246	neutral	None	None	None	None	N
E/T	0.2476	likely_benign	0.2287	benign	-0.113	Destabilizing	0.072	N	0.259	neutral	None	None	None	None	N
E/V	0.2906	likely_benign	0.2614	benign	0.037	Stabilizing	0.106	N	0.305	neutral	N	0.483155507	None	None	N
E/W	0.9319	likely_pathogenic	0.8994	pathogenic	0.045	Stabilizing	0.864	D	0.341	neutral	None	None	None	None	N
E/Y	0.6752	likely_pathogenic	0.5882	pathogenic	0.15	Stabilizing	0.628	D	0.301	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.