TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6308	19147;19148;19149	chr2:178729116;178729115;178729114	chr2:179593843;179593842;179593841
N2AB	5991	18196;18197;18198	chr2:178729116;178729115;178729114	chr2:179593843;179593842;179593841
N2A	5064	15415;15416;15417	chr2:178729116;178729115;178729114	chr2:179593843;179593842;179593841
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-47
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3359
• 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/P	rs1259623992	-0.801	0.523	N	0.401	0.159	0.101711395817	gnomAD-2.1.1	4.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.24E-06	0
S/P	rs1259623992	-0.801	0.523	N	0.401	0.159	0.101711395817	gnomAD-4.0.0	2.05991E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70388E-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
S/A	0.0703	likely_benign	0.0677	benign	-0.622	Destabilizing	0.001	N	0.102	neutral	N	0.448418497	None	None	N
S/C	0.1409	likely_benign	0.124	benign	-0.341	Destabilizing	0.794	D	0.385	neutral	N	0.47685147	None	None	N
S/D	0.3196	likely_benign	0.2844	benign	0.157	Stabilizing	0.002	N	0.153	neutral	None	None	None	None	N
S/E	0.3777	ambiguous	0.3504	ambiguous	0.069	Stabilizing	0.129	N	0.277	neutral	None	None	None	None	N
S/F	0.1367	likely_benign	0.1241	benign	-1.236	Destabilizing	0.655	D	0.431	neutral	N	0.46820419	None	None	N
S/G	0.1075	likely_benign	0.1071	benign	-0.73	Destabilizing	0.129	N	0.294	neutral	None	None	None	None	N
S/H	0.267	likely_benign	0.2465	benign	-1.294	Destabilizing	0.94	D	0.387	neutral	None	None	None	None	N
S/I	0.132	likely_benign	0.1164	benign	-0.46	Destabilizing	0.264	N	0.393	neutral	None	None	None	None	N
S/K	0.4372	ambiguous	0.4036	ambiguous	-0.407	Destabilizing	0.418	N	0.264	neutral	None	None	None	None	N
S/L	0.0761	likely_benign	0.073	benign	-0.46	Destabilizing	0.129	N	0.413	neutral	None	None	None	None	N
S/M	0.1728	likely_benign	0.1582	benign	-0.033	Destabilizing	0.027	N	0.289	neutral	None	None	None	None	N
S/N	0.136	likely_benign	0.1252	benign	-0.15	Destabilizing	0.264	N	0.253	neutral	None	None	None	None	N
S/P	0.0955	likely_benign	0.0963	benign	-0.487	Destabilizing	0.523	D	0.401	neutral	N	0.456267189	None	None	N
S/Q	0.3616	ambiguous	0.3371	benign	-0.462	Destabilizing	0.836	D	0.357	neutral	None	None	None	None	N
S/R	0.3604	ambiguous	0.3402	ambiguous	-0.218	Destabilizing	0.716	D	0.433	neutral	None	None	None	None	N
S/T	0.07	likely_benign	0.0671	benign	-0.307	Destabilizing	0.007	N	0.117	neutral	N	0.416092648	None	None	N
S/V	0.1274	likely_benign	0.1157	benign	-0.487	Destabilizing	0.01	N	0.275	neutral	None	None	None	None	N
S/W	0.2636	likely_benign	0.2568	benign	-1.168	Destabilizing	0.983	D	0.453	neutral	None	None	None	None	N
S/Y	0.1457	likely_benign	0.1342	benign	-0.905	Destabilizing	0.921	D	0.409	neutral	N	0.47659798	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.