TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18909	56950;56951;56952	chr2:178598985;178598984;178598983	chr2:179463712;179463711;179463710
N2AB	17268	52027;52028;52029	chr2:178598985;178598984;178598983	chr2:179463712;179463711;179463710
N2A	16341	49246;49247;49248	chr2:178598985;178598984;178598983	chr2:179463712;179463711;179463710
N2B	9844	29755;29756;29757	chr2:178598985;178598984;178598983	chr2:179463712;179463711;179463710
Novex-1	9969	30130;30131;30132	chr2:178598985;178598984;178598983	chr2:179463712;179463711;179463710
Novex-2	10036	30331;30332;30333	chr2:178598985;178598984;178598983	chr2:179463712;179463711;179463710
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-25
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8311
• 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
E/K	rs1224434103	0.541	0.116	N	0.111	0.239	0.244539031024	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.09E-06	0
E/K	rs1224434103	0.541	0.116	N	0.111	0.239	0.244539031024	gnomAD-4.0.0	4.11078E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.40073E-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
E/A	0.1294	likely_benign	0.1248	benign	-0.022	Destabilizing	0.906	D	0.353	neutral	N	0.476768252	None	None	I
E/C	0.7799	likely_pathogenic	0.7536	pathogenic	-0.362	Destabilizing	1.0	D	0.37	neutral	None	None	None	None	I
E/D	0.1355	likely_benign	0.1296	benign	-0.483	Destabilizing	0.906	D	0.357	neutral	N	0.470188996	None	None	I
E/F	0.7416	likely_pathogenic	0.7192	pathogenic	-0.056	Destabilizing	0.999	D	0.361	neutral	None	None	None	None	I
E/G	0.1896	likely_benign	0.1864	benign	-0.124	Destabilizing	0.979	D	0.405	neutral	N	0.472037223	None	None	I
E/H	0.4785	ambiguous	0.4582	ambiguous	0.626	Stabilizing	0.995	D	0.345	neutral	None	None	None	None	I
E/I	0.2694	likely_benign	0.2488	benign	0.187	Stabilizing	0.991	D	0.392	neutral	None	None	None	None	I
E/K	0.1419	likely_benign	0.1401	benign	0.329	Stabilizing	0.116	N	0.111	neutral	N	0.463414953	None	None	I
E/L	0.3302	likely_benign	0.3098	benign	0.187	Stabilizing	0.969	D	0.399	neutral	None	None	None	None	I
E/M	0.4213	ambiguous	0.4067	ambiguous	-0.123	Destabilizing	0.999	D	0.369	neutral	None	None	None	None	I
E/N	0.2788	likely_benign	0.2505	benign	0.022	Stabilizing	0.984	D	0.378	neutral	None	None	None	None	I
E/P	0.4485	ambiguous	0.4024	ambiguous	0.134	Stabilizing	0.999	D	0.361	neutral	None	None	None	None	I
E/Q	0.1415	likely_benign	0.1398	benign	0.028	Stabilizing	0.476	N	0.215	neutral	N	0.46844595	None	None	I
E/R	0.2461	likely_benign	0.2495	benign	0.596	Stabilizing	0.939	D	0.363	neutral	None	None	None	None	I
E/S	0.1944	likely_benign	0.1791	benign	-0.082	Destabilizing	0.864	D	0.335	neutral	None	None	None	None	I
E/T	0.1977	likely_benign	0.1747	benign	0.012	Stabilizing	0.293	N	0.288	neutral	None	None	None	None	I
E/V	0.1698	likely_benign	0.1605	benign	0.134	Stabilizing	0.959	D	0.431	neutral	N	0.477520401	None	None	I
E/W	0.8813	likely_pathogenic	0.877	pathogenic	-0.015	Destabilizing	1.0	D	0.411	neutral	None	None	None	None	I
E/Y	0.6078	likely_pathogenic	0.5901	pathogenic	0.161	Stabilizing	0.999	D	0.391	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.