TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21685	65278;65279;65280	chr2:178584498;178584497;178584496	chr2:179449225;179449224;179449223
N2AB	20044	60355;60356;60357	chr2:178584498;178584497;178584496	chr2:179449225;179449224;179449223
N2A	19117	57574;57575;57576	chr2:178584498;178584497;178584496	chr2:179449225;179449224;179449223
N2B	12620	38083;38084;38085	chr2:178584498;178584497;178584496	chr2:179449225;179449224;179449223
Novex-1	12745	38458;38459;38460	chr2:178584498;178584497;178584496	chr2:179449225;179449224;179449223
Novex-2	12812	38659;38660;38661	chr2:178584498;178584497;178584496	chr2:179449225;179449224;179449223
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-45
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4075
• 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/G	rs1335760990	-0.389	0.961	N	0.417	0.162	0.234412748748	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/G	rs1335760990	-0.389	0.961	N	0.417	0.162	0.234412748748	gnomAD-4.0.0	3.18492E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86632E-05	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	0.0927	likely_benign	0.0841	benign	-0.514	Destabilizing	0.931	D	0.453	neutral	None	None	None	None	I
S/C	0.106	likely_benign	0.0953	benign	-0.234	Destabilizing	1.0	D	0.532	neutral	N	0.469897073	None	None	I
S/D	0.2655	likely_benign	0.2663	benign	-0.088	Destabilizing	0.942	D	0.41	neutral	None	None	None	None	I
S/E	0.3992	ambiguous	0.3875	ambiguous	-0.19	Destabilizing	0.97	D	0.422	neutral	None	None	None	None	I
S/F	0.1788	likely_benign	0.1588	benign	-1.218	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
S/G	0.1186	likely_benign	0.1067	benign	-0.598	Destabilizing	0.961	D	0.417	neutral	N	0.476938824	None	None	I
S/H	0.2296	likely_benign	0.2293	benign	-1.215	Destabilizing	0.999	D	0.505	neutral	None	None	None	None	I
S/I	0.1552	likely_benign	0.1526	benign	-0.418	Destabilizing	0.989	D	0.661	neutral	N	0.465262264	None	None	I
S/K	0.4917	ambiguous	0.4971	ambiguous	-0.448	Destabilizing	0.97	D	0.425	neutral	None	None	None	None	I
S/L	0.1076	likely_benign	0.097	benign	-0.418	Destabilizing	0.97	D	0.555	neutral	None	None	None	None	I
S/M	0.1817	likely_benign	0.166	benign	0.063	Stabilizing	1.0	D	0.505	neutral	None	None	None	None	I
S/N	0.1182	likely_benign	0.1096	benign	-0.176	Destabilizing	0.248	N	0.264	neutral	N	0.432531898	None	None	I
S/P	0.8297	likely_pathogenic	0.8494	pathogenic	-0.424	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	I
S/Q	0.3887	ambiguous	0.3846	ambiguous	-0.502	Destabilizing	0.996	D	0.423	neutral	None	None	None	None	I
S/R	0.4269	ambiguous	0.4339	ambiguous	-0.231	Destabilizing	0.994	D	0.499	neutral	N	0.501565122	None	None	I
S/T	0.0739	likely_benign	0.0732	benign	-0.284	Destabilizing	0.248	N	0.209	neutral	N	0.492849639	None	None	I
S/V	0.1595	likely_benign	0.1505	benign	-0.424	Destabilizing	0.991	D	0.562	neutral	None	None	None	None	I
S/W	0.3288	likely_benign	0.3222	benign	-1.197	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
S/Y	0.1667	likely_benign	0.1554	benign	-0.921	Destabilizing	0.999	D	0.653	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.