TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23460	70603;70604;70605	chr2:178575754;178575753;178575752	chr2:179440481;179440480;179440479
N2AB	21819	65680;65681;65682	chr2:178575754;178575753;178575752	chr2:179440481;179440480;179440479
N2A	20892	62899;62900;62901	chr2:178575754;178575753;178575752	chr2:179440481;179440480;179440479
N2B	14395	43408;43409;43410	chr2:178575754;178575753;178575752	chr2:179440481;179440480;179440479
Novex-1	14520	43783;43784;43785	chr2:178575754;178575753;178575752	chr2:179440481;179440480;179440479
Novex-2	14587	43984;43985;43986	chr2:178575754;178575753;178575752	chr2:179440481;179440480;179440479
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-58
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8685
• 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
L/R	rs879027466	None	0.995	N	0.584	0.489	0.547979623877	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
L/R	rs879027466	None	0.995	N	0.584	0.489	0.547979623877	gnomAD-4.0.0	5.12638E-06	None	None	None	None	I	None	6.76888E-05	0	None	0	0	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
L/A	0.1917	likely_benign	0.2155	benign	-0.552	Destabilizing	0.971	D	0.503	neutral	None	None	None	None	I
L/C	0.5511	ambiguous	0.6222	pathogenic	-0.876	Destabilizing	1.0	D	0.521	neutral	None	None	None	None	I
L/D	0.6198	likely_pathogenic	0.6926	pathogenic	-0.301	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	I
L/E	0.2943	likely_benign	0.3598	ambiguous	-0.373	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	I
L/F	0.1986	likely_benign	0.2476	benign	-0.595	Destabilizing	0.99	D	0.466	neutral	None	None	None	None	I
L/G	0.5051	ambiguous	0.5616	ambiguous	-0.672	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
L/H	0.2837	likely_benign	0.3473	ambiguous	0.104	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	I
L/I	0.0885	likely_benign	0.0907	benign	-0.344	Destabilizing	0.006	N	0.145	neutral	None	None	None	None	I
L/K	0.2834	likely_benign	0.341	ambiguous	-0.42	Destabilizing	0.955	D	0.583	neutral	None	None	None	None	I
L/M	0.1083	likely_benign	0.1157	benign	-0.708	Destabilizing	0.955	D	0.462	neutral	N	0.487840425	None	None	I
L/N	0.3321	likely_benign	0.3517	ambiguous	-0.361	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
L/P	0.3502	ambiguous	0.4154	ambiguous	-0.386	Destabilizing	0.998	D	0.615	neutral	N	0.512726265	None	None	I
L/Q	0.1462	likely_benign	0.1801	benign	-0.514	Destabilizing	0.996	D	0.576	neutral	D	0.52221254	None	None	I
L/R	0.2601	likely_benign	0.3396	benign	0.058	Stabilizing	0.995	D	0.584	neutral	N	0.521345749	None	None	I
L/S	0.2582	likely_benign	0.3024	benign	-0.752	Destabilizing	0.996	D	0.519	neutral	None	None	None	None	I
L/T	0.2165	likely_benign	0.2327	benign	-0.721	Destabilizing	0.909	D	0.479	neutral	None	None	None	None	I
L/V	0.0825	likely_benign	0.0907	benign	-0.386	Destabilizing	0.013	N	0.177	neutral	N	0.4843103	None	None	I
L/W	0.4464	ambiguous	0.5514	ambiguous	-0.606	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
L/Y	0.4082	ambiguous	0.4723	ambiguous	-0.39	Destabilizing	0.971	D	0.469	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.