TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8269	25030;25031;25032	chr2:178718201;178718200;178718199	chr2:179582928;179582927;179582926
N2AB	7952	24079;24080;24081	chr2:178718201;178718200;178718199	chr2:179582928;179582927;179582926
N2A	7025	21298;21299;21300	chr2:178718201;178718200;178718199	chr2:179582928;179582927;179582926
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-68
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4535
• 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
P/L	rs960099770	None	0.011	N	0.412	0.239	None	gnomAD-4.0.0	1.62141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04507E-05

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
P/A	0.1015	likely_benign	0.1097	benign	-0.974	Destabilizing	0.025	N	0.335	neutral	N	0.489080733	None	None	N
P/C	0.6043	likely_pathogenic	0.6656	pathogenic	-0.619	Destabilizing	0.968	D	0.504	neutral	None	None	None	None	N
P/D	0.3849	ambiguous	0.4405	ambiguous	-0.532	Destabilizing	None	N	0.313	neutral	None	None	None	None	N
P/E	0.2352	likely_benign	0.2624	benign	-0.586	Destabilizing	0.029	N	0.437	neutral	None	None	None	None	N
P/F	0.5255	ambiguous	0.5625	ambiguous	-0.831	Destabilizing	0.891	D	0.553	neutral	None	None	None	None	N
P/G	0.3277	likely_benign	0.3504	ambiguous	-1.219	Destabilizing	0.279	N	0.441	neutral	None	None	None	None	N
P/H	0.1624	likely_benign	0.1755	benign	-0.732	Destabilizing	0.009	N	0.341	neutral	D	0.533102403	None	None	N
P/I	0.3923	ambiguous	0.4292	ambiguous	-0.441	Destabilizing	0.699	D	0.518	neutral	None	None	None	None	N
P/K	0.2145	likely_benign	0.2336	benign	-0.767	Destabilizing	0.059	N	0.305	neutral	None	None	None	None	N
P/L	0.1476	likely_benign	0.1668	benign	-0.441	Destabilizing	0.011	N	0.412	neutral	N	0.492043248	None	None	N
P/M	0.3584	ambiguous	0.3895	ambiguous	-0.365	Destabilizing	0.859	D	0.523	neutral	None	None	None	None	N
P/N	0.2875	likely_benign	0.3177	benign	-0.46	Destabilizing	0.366	N	0.526	neutral	None	None	None	None	N
P/Q	0.1399	likely_benign	0.1518	benign	-0.664	Destabilizing	0.635	D	0.549	neutral	None	None	None	None	N
P/R	0.144	likely_benign	0.1509	benign	-0.251	Destabilizing	0.637	D	0.583	neutral	N	0.503856932	None	None	N
P/S	0.1402	likely_benign	0.154	benign	-0.935	Destabilizing	0.016	N	0.201	neutral	D	0.523538771	None	None	N
P/T	0.1171	likely_benign	0.1316	benign	-0.883	Destabilizing	0.006	N	0.275	neutral	D	0.535910635	None	None	N
P/V	0.2665	likely_benign	0.2931	benign	-0.582	Destabilizing	0.011	N	0.377	neutral	None	None	None	None	N
P/W	0.6879	likely_pathogenic	0.7191	pathogenic	-0.954	Destabilizing	0.997	D	0.539	neutral	None	None	None	None	N
P/Y	0.4155	ambiguous	0.4473	ambiguous	-0.668	Destabilizing	0.942	D	0.578	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.