TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9289	28090;28091;28092	chr2:178711965;178711964;178711963	chr2:179576692;179576691;179576690
N2AB	8972	27139;27140;27141	chr2:178711965;178711964;178711963	chr2:179576692;179576691;179576690
N2A	8045	24358;24359;24360	chr2:178711965;178711964;178711963	chr2:179576692;179576691;179576690
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-78
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3533
• 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/P	rs2076724301	None	0.004	N	0.279	0.327	0.273938319068	gnomAD-4.0.0	8.09961E-06	None	None	None	None	I	None	0	0	None	0	1.39098E-04	None	0	0	0	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	0.0772	likely_benign	0.0884	benign	-0.459	Destabilizing	0.002	N	0.178	neutral	D	0.532443469	None	None	I
S/C	0.1608	likely_benign	0.1779	benign	-0.333	Destabilizing	0.977	D	0.561	neutral	None	None	None	None	I
S/D	0.4199	ambiguous	0.4312	ambiguous	0.409	Stabilizing	0.766	D	0.502	neutral	None	None	None	None	I
S/E	0.473	ambiguous	0.4866	ambiguous	0.346	Stabilizing	0.617	D	0.481	neutral	None	None	None	None	I
S/F	0.2072	likely_benign	0.2598	benign	-0.864	Destabilizing	0.92	D	0.655	neutral	None	None	None	None	I
S/G	0.105	likely_benign	0.1318	benign	-0.624	Destabilizing	0.25	N	0.47	neutral	None	None	None	None	I
S/H	0.2904	likely_benign	0.2776	benign	-1.067	Destabilizing	0.992	D	0.567	neutral	None	None	None	None	I
S/I	0.2044	likely_benign	0.2421	benign	-0.147	Destabilizing	0.85	D	0.671	neutral	None	None	None	None	I
S/K	0.3994	ambiguous	0.3666	ambiguous	-0.447	Destabilizing	0.617	D	0.471	neutral	None	None	None	None	I
S/L	0.1207	likely_benign	0.151	benign	-0.147	Destabilizing	0.379	N	0.64	neutral	N	0.498622932	None	None	I
S/M	0.242	likely_benign	0.2612	benign	-0.005	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	I
S/N	0.1374	likely_benign	0.1448	benign	-0.214	Destabilizing	0.766	D	0.527	neutral	None	None	None	None	I
S/P	0.2865	likely_benign	0.3897	ambiguous	-0.22	Destabilizing	0.004	N	0.279	neutral	N	0.500028511	None	None	I
S/Q	0.3975	ambiguous	0.3807	ambiguous	-0.407	Destabilizing	0.92	D	0.537	neutral	None	None	None	None	I
S/R	0.3271	likely_benign	0.331	benign	-0.302	Destabilizing	0.85	D	0.601	neutral	None	None	None	None	I
S/T	0.0867	likely_benign	0.0953	benign	-0.337	Destabilizing	0.334	N	0.473	neutral	N	0.46289017	None	None	I
S/V	0.183	likely_benign	0.2177	benign	-0.22	Destabilizing	0.447	N	0.631	neutral	None	None	None	None	I
S/W	0.3773	ambiguous	0.4659	ambiguous	-0.841	Destabilizing	0.992	D	0.692	prob.neutral	None	None	None	None	I
S/Y	0.1923	likely_benign	0.2321	benign	-0.569	Destabilizing	0.972	D	0.649	neutral	None	None	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.