TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17950	54073;54074;54075	chr2:178605447;178605446;178605445	chr2:179470174;179470173;179470172
N2AB	16309	49150;49151;49152	chr2:178605447;178605446;178605445	chr2:179470174;179470173;179470172
N2A	15382	46369;46370;46371	chr2:178605447;178605446;178605445	chr2:179470174;179470173;179470172
N2B	8885	26878;26879;26880	chr2:178605447;178605446;178605445	chr2:179470174;179470173;179470172
Novex-1	9010	27253;27254;27255	chr2:178605447;178605446;178605445	chr2:179470174;179470173;179470172
Novex-2	9077	27454;27455;27456	chr2:178605447;178605446;178605445	chr2:179470174;179470173;179470172
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-18
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.9835
• 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	rs2054558907	None	0.988	N	0.815	0.337	0.602722737475	gnomAD-4.0.0	1.60013E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87527E-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
L/A	0.4215	ambiguous	0.3983	ambiguous	-0.438	Destabilizing	0.168	N	0.441	neutral	None	None	None	None	I
L/C	0.7856	likely_pathogenic	0.751	pathogenic	-0.7	Destabilizing	0.999	D	0.658	prob.neutral	None	None	None	None	I
L/D	0.8528	likely_pathogenic	0.823	pathogenic	-0.12	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	I
L/E	0.602	likely_pathogenic	0.5775	pathogenic	-0.22	Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	I
L/F	0.277	likely_benign	0.2411	benign	-0.589	Destabilizing	0.991	D	0.598	neutral	None	None	None	None	I
L/G	0.7525	likely_pathogenic	0.7385	pathogenic	-0.549	Destabilizing	0.981	D	0.572	neutral	None	None	None	None	I
L/H	0.4759	ambiguous	0.4438	ambiguous	0.081	Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
L/I	0.1247	likely_benign	0.1186	benign	-0.272	Destabilizing	0.132	N	0.181	neutral	N	0.419333315	None	None	I
L/K	0.4561	ambiguous	0.4531	ambiguous	-0.259	Destabilizing	0.991	D	0.73	deleterious	None	None	None	None	I
L/M	0.1611	likely_benign	0.1574	benign	-0.472	Destabilizing	0.991	D	0.616	neutral	None	None	None	None	I
L/N	0.5358	ambiguous	0.5007	ambiguous	-0.089	Destabilizing	0.997	D	0.813	deleterious	None	None	None	None	I
L/P	0.5385	ambiguous	0.5144	ambiguous	-0.297	Destabilizing	0.988	D	0.804	deleterious	N	0.403958431	None	None	I
L/Q	0.299	likely_benign	0.2998	benign	-0.288	Destabilizing	0.996	D	0.818	deleterious	N	0.42683529	None	None	I
L/R	0.4324	ambiguous	0.4156	ambiguous	0.222	Stabilizing	0.988	D	0.815	deleterious	N	0.449616149	None	None	I
L/S	0.5118	ambiguous	0.4852	ambiguous	-0.496	Destabilizing	0.883	D	0.598	neutral	None	None	None	None	I
L/T	0.4239	ambiguous	0.4055	ambiguous	-0.491	Destabilizing	0.938	D	0.628	neutral	None	None	None	None	I
L/V	0.15	likely_benign	0.1439	benign	-0.297	Destabilizing	0.702	D	0.586	neutral	N	0.435590846	None	None	I
L/W	0.5471	ambiguous	0.5026	ambiguous	-0.605	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	I
L/Y	0.5369	ambiguous	0.4986	ambiguous	-0.356	Destabilizing	0.997	D	0.633	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.