TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27776	83551;83552;83553	chr2:178562806;178562805;178562804	chr2:179427533;179427532;179427531
N2AB	26135	78628;78629;78630	chr2:178562806;178562805;178562804	chr2:179427533;179427532;179427531
N2A	25208	75847;75848;75849	chr2:178562806;178562805;178562804	chr2:179427533;179427532;179427531
N2B	18711	56356;56357;56358	chr2:178562806;178562805;178562804	chr2:179427533;179427532;179427531
Novex-1	18836	56731;56732;56733	chr2:178562806;178562805;178562804	chr2:179427533;179427532;179427531
Novex-2	18903	56932;56933;56934	chr2:178562806;178562805;178562804	chr2:179427533;179427532;179427531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-90
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.7299
• 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
R/K	rs2154160964	None	None	N	0.142	0.064	0.0954503805726	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.2579	likely_benign	0.272	benign	-0.264	Destabilizing	0.055	N	0.359	neutral	None	None	None	None	N
R/C	0.1442	likely_benign	0.1618	benign	-0.224	Destabilizing	0.883	D	0.361	neutral	None	None	None	None	N
R/D	0.5441	ambiguous	0.5712	pathogenic	-0.062	Destabilizing	0.22	N	0.468	neutral	None	None	None	None	N
R/E	0.2885	likely_benign	0.3054	benign	-0.005	Destabilizing	0.055	N	0.423	neutral	None	None	None	None	N
R/F	0.4736	ambiguous	0.5001	ambiguous	-0.48	Destabilizing	0.667	D	0.402	neutral	None	None	None	None	N
R/G	0.1671	likely_benign	0.178	benign	-0.47	Destabilizing	0.042	N	0.429	neutral	N	0.425840786	None	None	N
R/H	0.0898	likely_benign	0.0962	benign	-0.859	Destabilizing	0.667	D	0.493	neutral	None	None	None	None	N
R/I	0.2365	likely_benign	0.2444	benign	0.251	Stabilizing	0.272	N	0.415	neutral	N	0.421837689	None	None	N
R/K	0.0719	likely_benign	0.0692	benign	-0.233	Destabilizing	None	N	0.142	neutral	N	0.324444428	None	None	N
R/L	0.2013	likely_benign	0.2182	benign	0.251	Stabilizing	0.124	N	0.456	neutral	None	None	None	None	N
R/M	0.2103	likely_benign	0.2217	benign	0.029	Stabilizing	0.667	D	0.417	neutral	None	None	None	None	N
R/N	0.405	ambiguous	0.42	ambiguous	0.207	Stabilizing	0.22	N	0.431	neutral	None	None	None	None	N
R/P	0.7255	likely_pathogenic	0.7613	pathogenic	0.1	Stabilizing	0.364	N	0.45	neutral	None	None	None	None	N
R/Q	0.0865	likely_benign	0.0927	benign	-0.024	Destabilizing	0.124	N	0.444	neutral	None	None	None	None	N
R/S	0.306	likely_benign	0.3299	benign	-0.32	Destabilizing	0.003	N	0.221	neutral	N	0.347779861	None	None	N
R/T	0.1377	likely_benign	0.1453	benign	-0.128	Destabilizing	0.001	N	0.225	neutral	N	0.334101274	None	None	N
R/V	0.2678	likely_benign	0.2733	benign	0.1	Stabilizing	0.124	N	0.466	neutral	None	None	None	None	N
R/W	0.1775	likely_benign	0.1976	benign	-0.401	Destabilizing	0.958	D	0.387	neutral	None	None	None	None	N
R/Y	0.3343	likely_benign	0.3494	ambiguous	-0.016	Destabilizing	0.667	D	0.417	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.