TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23940	72043;72044;72045	chr2:178574314;178574313;178574312	chr2:179439041;179439040;179439039
N2AB	22299	67120;67121;67122	chr2:178574314;178574313;178574312	chr2:179439041;179439040;179439039
N2A	21372	64339;64340;64341	chr2:178574314;178574313;178574312	chr2:179439041;179439040;179439039
N2B	14875	44848;44849;44850	chr2:178574314;178574313;178574312	chr2:179439041;179439040;179439039
Novex-1	15000	45223;45224;45225	chr2:178574314;178574313;178574312	chr2:179439041;179439040;179439039
Novex-2	15067	45424;45425;45426	chr2:178574314;178574313;178574312	chr2:179439041;179439040;179439039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-62
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.3
• 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
T/I	rs1553610793	None	0.491	N	0.565	0.279	0.382761230579	gnomAD-4.0.0	3.18354E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	2.77932E-05	None	0	0	0	0	0
T/R	None	None	0.491	D	0.503	0.259	0.508046185061	gnomAD-4.0.0	3.18354E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85896E-06	1.43308E-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
T/A	0.073	likely_benign	0.0713	benign	-0.767	Destabilizing	None	N	0.084	neutral	N	0.465321894	None	None	N
T/C	0.3634	ambiguous	0.3598	ambiguous	-0.894	Destabilizing	0.901	D	0.583	neutral	None	None	None	None	N
T/D	0.3984	ambiguous	0.429	ambiguous	-1.569	Destabilizing	0.209	N	0.413	neutral	None	None	None	None	N
T/E	0.299	likely_benign	0.3182	benign	-1.513	Destabilizing	0.007	N	0.241	neutral	None	None	None	None	N
T/F	0.2544	likely_benign	0.2579	benign	-0.943	Destabilizing	0.901	D	0.607	neutral	None	None	None	None	N
T/G	0.2326	likely_benign	0.2505	benign	-1.039	Destabilizing	0.209	N	0.399	neutral	None	None	None	None	N
T/H	0.2505	likely_benign	0.2542	benign	-1.404	Destabilizing	0.965	D	0.601	neutral	None	None	None	None	N
T/I	0.2617	likely_benign	0.2646	benign	-0.119	Destabilizing	0.491	N	0.565	neutral	N	0.485362117	None	None	N
T/K	0.3052	likely_benign	0.3176	benign	-0.756	Destabilizing	0.285	N	0.414	neutral	N	0.516422718	None	None	N
T/L	0.1269	likely_benign	0.124	benign	-0.119	Destabilizing	0.209	N	0.417	neutral	None	None	None	None	N
T/M	0.0886	likely_benign	0.0863	benign	0.146	Stabilizing	0.965	D	0.589	neutral	None	None	None	None	N
T/N	0.1307	likely_benign	0.1396	benign	-1.123	Destabilizing	0.561	D	0.411	neutral	None	None	None	None	N
T/P	0.8785	likely_pathogenic	0.8882	pathogenic	-0.304	Destabilizing	0.662	D	0.517	neutral	N	0.508074728	None	None	N
T/Q	0.2311	likely_benign	0.2347	benign	-1.309	Destabilizing	0.561	D	0.498	neutral	None	None	None	None	N
T/R	0.2557	likely_benign	0.2534	benign	-0.558	Destabilizing	0.491	N	0.503	neutral	D	0.523138047	None	None	N
T/S	0.0813	likely_benign	0.0856	benign	-1.213	Destabilizing	0.002	N	0.084	neutral	N	0.365824117	None	None	N
T/V	0.1818	likely_benign	0.1802	benign	-0.304	Destabilizing	0.209	N	0.369	neutral	None	None	None	None	N
T/W	0.6256	likely_pathogenic	0.6351	pathogenic	-1.001	Destabilizing	0.991	D	0.61	neutral	None	None	None	None	N
T/Y	0.2841	likely_benign	0.2921	benign	-0.638	Destabilizing	0.965	D	0.607	neutral	None	None	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.