TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7863	23812;23813;23814	chr2:178720055;178720054;178720053	chr2:179584782;179584781;179584780
N2AB	7546	22861;22862;22863	chr2:178720055;178720054;178720053	chr2:179584782;179584781;179584780
N2A	6619	20080;20081;20082	chr2:178720055;178720054;178720053	chr2:179584782;179584781;179584780
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-63
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2492
• 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	rs1553906488	None	0.794	D	0.56	0.463	0.259761712551	gnomAD-4.0.0	4.10585E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39739E-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	0.0674	likely_benign	0.0612	benign	-0.833	Destabilizing	0.001	N	0.145	neutral	N	0.435223566	None	None	N
S/C	0.1712	likely_benign	0.139	benign	-0.536	Destabilizing	0.794	D	0.527	neutral	D	0.527135668	None	None	N
S/D	0.455	ambiguous	0.4438	ambiguous	0.027	Stabilizing	0.593	D	0.447	neutral	None	None	None	None	N
S/E	0.5143	ambiguous	0.5049	ambiguous	-0.018	Destabilizing	0.418	N	0.437	neutral	None	None	None	None	N
S/F	0.2989	likely_benign	0.2535	benign	-1.296	Destabilizing	0.001	N	0.295	neutral	N	0.511905022	None	None	N
S/G	0.0836	likely_benign	0.0776	benign	-1.004	Destabilizing	0.001	N	0.138	neutral	None	None	None	None	N
S/H	0.4185	ambiguous	0.3953	ambiguous	-1.518	Destabilizing	0.94	D	0.533	neutral	None	None	None	None	N
S/I	0.2116	likely_benign	0.1857	benign	-0.491	Destabilizing	0.264	N	0.531	neutral	None	None	None	None	N
S/K	0.6186	likely_pathogenic	0.6102	pathogenic	-0.53	Destabilizing	0.418	N	0.427	neutral	None	None	None	None	N
S/L	0.131	likely_benign	0.1167	benign	-0.491	Destabilizing	0.129	N	0.417	neutral	None	None	None	None	N
S/M	0.2656	likely_benign	0.2318	benign	-0.084	Destabilizing	0.836	D	0.541	neutral	None	None	None	None	N
S/N	0.1736	likely_benign	0.1649	benign	-0.393	Destabilizing	0.418	N	0.483	neutral	None	None	None	None	N
S/P	0.5527	ambiguous	0.4666	ambiguous	-0.576	Destabilizing	0.794	D	0.56	neutral	D	0.538149578	None	None	N
S/Q	0.4844	ambiguous	0.4705	ambiguous	-0.65	Destabilizing	0.836	D	0.521	neutral	None	None	None	None	N
S/R	0.4602	ambiguous	0.4716	ambiguous	-0.376	Destabilizing	0.836	D	0.565	neutral	None	None	None	None	N
S/T	0.0982	likely_benign	0.0879	benign	-0.527	Destabilizing	0.183	N	0.448	neutral	N	0.512569629	None	None	N
S/V	0.2295	likely_benign	0.1957	benign	-0.576	Destabilizing	0.002	N	0.322	neutral	None	None	None	None	N
S/W	0.4711	ambiguous	0.434	ambiguous	-1.2	Destabilizing	0.983	D	0.557	neutral	None	None	None	None	N
S/Y	0.2644	likely_benign	0.2301	benign	-0.946	Destabilizing	0.487	N	0.581	neutral	N	0.520298813	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.