TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19304	58135;58136;58137	chr2:178594584;178594583;178594582	chr2:179459311;179459310;179459309
N2AB	17663	53212;53213;53214	chr2:178594584;178594583;178594582	chr2:179459311;179459310;179459309
N2A	16736	50431;50432;50433	chr2:178594584;178594583;178594582	chr2:179459311;179459310;179459309
N2B	10239	30940;30941;30942	chr2:178594584;178594583;178594582	chr2:179459311;179459310;179459309
Novex-1	10364	31315;31316;31317	chr2:178594584;178594583;178594582	chr2:179459311;179459310;179459309
Novex-2	10431	31516;31517;31518	chr2:178594584;178594583;178594582	chr2:179459311;179459310;179459309
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-28
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2139
• 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
T/P	None	None	0.966	N	0.45	0.397	0.457197642564	gnomAD-4.0.0	3.42283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.499E-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
T/A	0.1018	likely_benign	0.0911	benign	-1.056	Destabilizing	0.022	N	0.212	neutral	N	0.453931465	None	None	N
T/C	0.3335	likely_benign	0.3557	ambiguous	-0.78	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
T/D	0.5515	ambiguous	0.458	ambiguous	-1.622	Destabilizing	0.842	D	0.379	neutral	None	None	None	None	N
T/E	0.3727	ambiguous	0.3275	benign	-1.431	Destabilizing	0.842	D	0.381	neutral	None	None	None	None	N
T/F	0.2509	likely_benign	0.2201	benign	-0.531	Destabilizing	0.991	D	0.569	neutral	None	None	None	None	N
T/G	0.2528	likely_benign	0.2594	benign	-1.476	Destabilizing	0.525	D	0.441	neutral	None	None	None	None	N
T/H	0.2962	likely_benign	0.2702	benign	-1.62	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	N
T/I	0.1804	likely_benign	0.1597	benign	0.047	Stabilizing	0.966	D	0.439	neutral	N	0.476461347	None	None	N
T/K	0.3517	ambiguous	0.2988	benign	-0.806	Destabilizing	0.842	D	0.384	neutral	None	None	None	None	N
T/L	0.121	likely_benign	0.1075	benign	0.047	Stabilizing	0.842	D	0.412	neutral	None	None	None	None	N
T/M	0.1016	likely_benign	0.0926	benign	0.033	Stabilizing	0.991	D	0.477	neutral	None	None	None	None	N
T/N	0.1671	likely_benign	0.1516	benign	-1.439	Destabilizing	0.801	D	0.354	neutral	N	0.467925744	None	None	N
T/P	0.8854	likely_pathogenic	0.8177	pathogenic	-0.289	Destabilizing	0.966	D	0.45	neutral	N	0.51596154	None	None	N
T/Q	0.2613	likely_benign	0.2485	benign	-1.187	Destabilizing	0.974	D	0.453	neutral	None	None	None	None	N
T/R	0.313	likely_benign	0.2543	benign	-0.996	Destabilizing	0.949	D	0.451	neutral	None	None	None	None	N
T/S	0.1047	likely_benign	0.1051	benign	-1.604	Destabilizing	0.022	N	0.235	neutral	N	0.421968188	None	None	N
T/V	0.1527	likely_benign	0.1451	benign	-0.289	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	N
T/W	0.6508	likely_pathogenic	0.5891	pathogenic	-0.765	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
T/Y	0.3171	likely_benign	0.2865	benign	-0.403	Destabilizing	0.991	D	0.568	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.