TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3840	11743;11744;11745	chr2:178741715;178741714;178741713	chr2:179606442;179606441;179606440
N2AB	3523	10792;10793;10794	chr2:178741715;178741714;178741713	chr2:179606442;179606441;179606440
N2A	None	None	chr2:None	chr2:None
N2B	3477	10654;10655;10656	chr2:178741715;178741714;178741713	chr2:179606442;179606441;179606440
Novex-1	3602	11029;11030;11031	chr2:178741715;178741714;178741713	chr2:179606442;179606441;179606440
Novex-2	3669	11230;11231;11232	chr2:178741715;178741714;178741713	chr2:179606442;179606441;179606440
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-27
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2877
• Predicted PPI site: I

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/C	None	None	0.001	N	0.401	0.223	None	gnomAD-4.0.0	6.84241E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15939E-05	0
S/F	None	None	None	N	0.542	0.221	None	gnomAD-4.0.0	6.84241E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99497E-07	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	0.0852	likely_benign	0.0869	benign	-1.016	Destabilizing	0.012	N	0.359	neutral	N	0.473170162	None	None	I
S/C	0.1365	likely_benign	0.1428	benign	-0.746	Destabilizing	0.001	N	0.401	neutral	N	0.514023897	None	None	I
S/D	0.496	ambiguous	0.5107	ambiguous	-0.395	Destabilizing	0.262	N	0.475	neutral	None	None	None	None	I
S/E	0.5411	ambiguous	0.5783	pathogenic	-0.359	Destabilizing	0.262	N	0.477	neutral	None	None	None	None	I
S/F	0.2028	likely_benign	0.205	benign	-1.189	Destabilizing	None	N	0.542	neutral	N	0.515715411	None	None	I
S/G	0.1744	likely_benign	0.1585	benign	-1.287	Destabilizing	0.149	N	0.478	neutral	None	None	None	None	I
S/H	0.3372	likely_benign	0.3613	ambiguous	-1.708	Destabilizing	0.791	D	0.572	neutral	None	None	None	None	I
S/I	0.2767	likely_benign	0.2735	benign	-0.383	Destabilizing	0.081	N	0.557	neutral	None	None	None	None	I
S/K	0.6149	likely_pathogenic	0.6266	pathogenic	-0.607	Destabilizing	0.149	N	0.473	neutral	None	None	None	None	I
S/L	0.1382	likely_benign	0.1276	benign	-0.383	Destabilizing	0.035	N	0.537	neutral	None	None	None	None	I
S/M	0.2912	likely_benign	0.2805	benign	-0.103	Destabilizing	0.555	D	0.575	neutral	None	None	None	None	I
S/N	0.2277	likely_benign	0.2017	benign	-0.693	Destabilizing	0.149	N	0.498	neutral	None	None	None	None	I
S/P	0.2571	likely_benign	0.4133	ambiguous	-0.561	Destabilizing	0.484	N	0.562	neutral	N	0.490519399	None	None	I
S/Q	0.5113	ambiguous	0.5437	ambiguous	-0.82	Destabilizing	0.555	D	0.502	neutral	None	None	None	None	I
S/R	0.5083	ambiguous	0.5067	ambiguous	-0.585	Destabilizing	0.555	D	0.557	neutral	None	None	None	None	I
S/T	0.1104	likely_benign	0.1025	benign	-0.718	Destabilizing	0.001	N	0.288	neutral	N	0.421117153	None	None	I
S/V	0.2796	likely_benign	0.2759	benign	-0.561	Destabilizing	0.081	N	0.581	neutral	None	None	None	None	I
S/W	0.3294	likely_benign	0.3822	ambiguous	-1.115	Destabilizing	0.824	D	0.678	prob.neutral	None	None	None	None	I
S/Y	0.1811	likely_benign	0.1932	benign	-0.84	Destabilizing	0.188	N	0.605	neutral	N	0.513173358	None	None	I

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.