TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29069	87430;87431;87432	chr2:178558149;178558148;178558147	chr2:179422876;179422875;179422874
N2AB	27428	82507;82508;82509	chr2:178558149;178558148;178558147	chr2:179422876;179422875;179422874
N2A	26501	79726;79727;79728	chr2:178558149;178558148;178558147	chr2:179422876;179422875;179422874
N2B	20004	60235;60236;60237	chr2:178558149;178558148;178558147	chr2:179422876;179422875;179422874
Novex-1	20129	60610;60611;60612	chr2:178558149;178558148;178558147	chr2:179422876;179422875;179422874
Novex-2	20196	60811;60812;60813	chr2:178558149;178558148;178558147	chr2:179422876;179422875;179422874
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-145
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3754
• 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	None	None	0.794	N	0.369	0.464	0.304108284078	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85789E-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	0.0676	likely_benign	0.069	benign	-0.111	Destabilizing	0.001	N	0.105	neutral	N	0.503179354	None	None	N
S/C	0.0888	likely_benign	0.0827	benign	-0.51	Destabilizing	0.794	D	0.335	neutral	N	0.491723625	None	None	N
S/D	0.4832	ambiguous	0.4492	ambiguous	0.018	Stabilizing	0.593	D	0.305	neutral	None	None	None	None	N
S/E	0.5011	ambiguous	0.4573	ambiguous	-0.082	Destabilizing	0.418	N	0.287	neutral	None	None	None	None	N
S/F	0.1188	likely_benign	0.1069	benign	-0.886	Destabilizing	0.002	N	0.313	neutral	D	0.529347235	None	None	N
S/G	0.1063	likely_benign	0.1065	benign	-0.147	Destabilizing	0.129	N	0.295	neutral	None	None	None	None	N
S/H	0.219	likely_benign	0.191	benign	-0.422	Destabilizing	0.94	D	0.338	neutral	None	None	None	None	N
S/I	0.1058	likely_benign	0.1089	benign	-0.149	Destabilizing	0.264	N	0.362	neutral	None	None	None	None	N
S/K	0.4202	ambiguous	0.3794	ambiguous	-0.384	Destabilizing	0.418	N	0.296	neutral	None	None	None	None	N
S/L	0.0722	likely_benign	0.0732	benign	-0.149	Destabilizing	0.129	N	0.342	neutral	None	None	None	None	N
S/M	0.1326	likely_benign	0.1357	benign	-0.274	Destabilizing	0.061	N	0.265	neutral	None	None	None	None	N
S/N	0.1474	likely_benign	0.1461	benign	-0.241	Destabilizing	0.593	D	0.363	neutral	None	None	None	None	N
S/P	0.8816	likely_pathogenic	0.8531	pathogenic	-0.113	Destabilizing	0.794	D	0.369	neutral	N	0.491216646	None	None	N
S/Q	0.3622	ambiguous	0.3312	benign	-0.414	Destabilizing	0.836	D	0.376	neutral	None	None	None	None	N
S/R	0.3362	likely_benign	0.2921	benign	-0.152	Destabilizing	0.716	D	0.369	neutral	None	None	None	None	N
S/T	0.0599	likely_benign	0.0635	benign	-0.32	Destabilizing	0.003	N	0.096	neutral	N	0.432817979	None	None	N
S/V	0.1233	likely_benign	0.1242	benign	-0.113	Destabilizing	0.129	N	0.341	neutral	None	None	None	None	N
S/W	0.2555	likely_benign	0.209	benign	-1.007	Destabilizing	0.983	D	0.445	neutral	None	None	None	None	N
S/Y	0.1354	likely_benign	0.1178	benign	-0.667	Destabilizing	0.487	N	0.407	neutral	N	0.491216646	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.