TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30721	92386;92387;92388	chr2:178549465;178549464;178549463	chr2:179414192;179414191;179414190
N2AB	29080	87463;87464;87465	chr2:178549465;178549464;178549463	chr2:179414192;179414191;179414190
N2A	28153	84682;84683;84684	chr2:178549465;178549464;178549463	chr2:179414192;179414191;179414190
N2B	21656	65191;65192;65193	chr2:178549465;178549464;178549463	chr2:179414192;179414191;179414190
Novex-1	21781	65566;65567;65568	chr2:178549465;178549464;178549463	chr2:179414192;179414191;179414190
Novex-2	21848	65767;65768;65769	chr2:178549465;178549464;178549463	chr2:179414192;179414191;179414190
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-112
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.615
• 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
D/A	None	None	1.0	N	0.843	0.462	0.478605750892	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
D/A	0.0917	likely_benign	0.1079	benign	-0.283	Destabilizing	1.0	D	0.843	deleterious	N	0.489678834	None	None	N
D/C	0.4422	ambiguous	0.4916	ambiguous	-0.103	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
D/E	0.1267	likely_benign	0.1608	benign	-0.78	Destabilizing	1.0	D	0.672	neutral	N	0.521636537	None	None	N
D/F	0.5261	ambiguous	0.6514	pathogenic	-0.306	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
D/G	0.0943	likely_benign	0.0975	benign	-0.592	Destabilizing	1.0	D	0.837	deleterious	N	0.376913476	None	None	N
D/H	0.2115	likely_benign	0.2542	benign	-0.759	Destabilizing	1.0	D	0.879	deleterious	N	0.495717691	None	None	N
D/I	0.368	ambiguous	0.4965	ambiguous	0.511	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
D/K	0.2789	likely_benign	0.3253	benign	-0.349	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
D/L	0.2808	likely_benign	0.3468	ambiguous	0.511	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
D/M	0.4631	ambiguous	0.5685	pathogenic	0.886	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
D/N	0.079	likely_benign	0.0991	benign	-0.593	Destabilizing	1.0	D	0.845	deleterious	N	0.476599478	None	None	N
D/P	0.7887	likely_pathogenic	0.8432	pathogenic	0.273	Stabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
D/Q	0.2386	likely_benign	0.2926	benign	-0.489	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
D/R	0.3186	likely_benign	0.3826	ambiguous	-0.342	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
D/S	0.0749	likely_benign	0.0835	benign	-0.81	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/T	0.1624	likely_benign	0.2017	benign	-0.57	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
D/V	0.2096	likely_benign	0.273	benign	0.273	Stabilizing	1.0	D	0.872	deleterious	N	0.495210712	None	None	N
D/W	0.8627	likely_pathogenic	0.9171	pathogenic	-0.309	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
D/Y	0.232	likely_benign	0.2859	benign	-0.117	Destabilizing	1.0	D	0.867	deleterious	N	0.506985091	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.