TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25515	76768;76769;76770	chr2:178569589;178569588;178569587	chr2:179434316;179434315;179434314
N2AB	23874	71845;71846;71847	chr2:178569589;178569588;178569587	chr2:179434316;179434315;179434314
N2A	22947	69064;69065;69066	chr2:178569589;178569588;178569587	chr2:179434316;179434315;179434314
N2B	16450	49573;49574;49575	chr2:178569589;178569588;178569587	chr2:179434316;179434315;179434314
Novex-1	16575	49948;49949;49950	chr2:178569589;178569588;178569587	chr2:179434316;179434315;179434314
Novex-2	16642	50149;50150;50151	chr2:178569589;178569588;178569587	chr2:179434316;179434315;179434314
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: Ig-135
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.9222
• 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/K	rs755797898	0.602	0.684	N	0.477	0.251	0.331876078066	gnomAD-2.1.1	8.12E-06	None	None	None	None	N	None	0	0	None	0	1.13636E-04	None	0	None	0	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
E/A	0.3927	ambiguous	0.4116	ambiguous	-0.186	Destabilizing	0.007	N	0.26	neutral	N	0.454227827	None	None	N
E/C	0.9575	likely_pathogenic	0.96	pathogenic	-0.359	Destabilizing	0.987	D	0.432	neutral	None	None	None	None	N
E/D	0.1137	likely_benign	0.1167	benign	-0.316	Destabilizing	0.001	N	0.173	neutral	N	0.384847887	None	None	N
E/F	0.9402	likely_pathogenic	0.944	pathogenic	0.059	Stabilizing	0.953	D	0.413	neutral	None	None	None	None	N
E/G	0.4115	ambiguous	0.4231	ambiguous	-0.363	Destabilizing	0.521	D	0.431	neutral	D	0.522164973	None	None	N
E/H	0.7959	likely_pathogenic	0.8178	pathogenic	0.642	Stabilizing	0.984	D	0.446	neutral	None	None	None	None	N
E/I	0.815	likely_pathogenic	0.8223	pathogenic	0.244	Stabilizing	0.91	D	0.418	neutral	None	None	None	None	N
E/K	0.6943	likely_pathogenic	0.7067	pathogenic	0.331	Stabilizing	0.684	D	0.477	neutral	N	0.460132292	None	None	N
E/L	0.7664	likely_pathogenic	0.7876	pathogenic	0.244	Stabilizing	0.59	D	0.406	neutral	None	None	None	None	N
E/M	0.8367	likely_pathogenic	0.8451	pathogenic	0.009	Stabilizing	0.996	D	0.419	neutral	None	None	None	None	N
E/N	0.4766	ambiguous	0.4853	ambiguous	-0.168	Destabilizing	0.742	D	0.452	neutral	None	None	None	None	N
E/P	0.8056	likely_pathogenic	0.852	pathogenic	0.12	Stabilizing	0.953	D	0.42	neutral	None	None	None	None	N
E/Q	0.4003	ambiguous	0.4231	ambiguous	-0.097	Destabilizing	0.815	D	0.457	neutral	N	0.521298181	None	None	N
E/R	0.7751	likely_pathogenic	0.7861	pathogenic	0.688	Stabilizing	0.953	D	0.438	neutral	None	None	None	None	N
E/S	0.3924	ambiguous	0.4089	ambiguous	-0.294	Destabilizing	0.59	D	0.449	neutral	None	None	None	None	N
E/T	0.5574	ambiguous	0.5686	pathogenic	-0.13	Destabilizing	0.742	D	0.445	neutral	None	None	None	None	N
E/V	0.6025	likely_pathogenic	0.6157	pathogenic	0.12	Stabilizing	0.521	D	0.409	neutral	D	0.522338331	None	None	N
E/W	0.9803	likely_pathogenic	0.9818	pathogenic	0.209	Stabilizing	0.996	D	0.532	neutral	None	None	None	None	N
E/Y	0.8675	likely_pathogenic	0.8827	pathogenic	0.303	Stabilizing	0.984	D	0.418	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.