TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35709	107350;107351;107352	chr2:178528626;178528625;178528624	chr2:179393353;179393352;179393351
N2AB	34068	102427;102428;102429	chr2:178528626;178528625;178528624	chr2:179393353;179393352;179393351
N2A	33141	99646;99647;99648	chr2:178528626;178528625;178528624	chr2:179393353;179393352;179393351
N2B	26644	80155;80156;80157	chr2:178528626;178528625;178528624	chr2:179393353;179393352;179393351
Novex-1	26769	80530;80531;80532	chr2:178528626;178528625;178528624	chr2:179393353;179393352;179393351
Novex-2	26836	80731;80732;80733	chr2:178528626;178528625;178528624	chr2:179393353;179393352;179393351
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: Ig-168
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6658
• 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
R/G	None	None	0.324	N	0.538	0.221	0.511390160789	gnomAD-4.0.0	1.59407E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43711E-05	0
R/K	None	None	0.001	N	0.147	0.093	0.12205267543	gnomAD-4.0.0	6.84751E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9991E-07	0	0
R/S	rs1687614865	None	0.193	N	0.507	0.188	0.234412748748	gnomAD-4.0.0	6.84731E-07	None	None	None	None	I	None	2.98793E-05	0	None	0	0	None	0	0	0	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	0.3002	likely_benign	0.3236	benign	0.022	Stabilizing	0.116	N	0.484	neutral	None	None	None	None	I
R/C	0.2928	likely_benign	0.3526	ambiguous	-0.177	Destabilizing	0.981	D	0.56	neutral	None	None	None	None	I
R/D	0.6139	likely_pathogenic	0.6684	pathogenic	-0.147	Destabilizing	0.388	N	0.563	neutral	None	None	None	None	I
R/E	0.2708	likely_benign	0.3113	benign	-0.09	Destabilizing	0.116	N	0.487	neutral	None	None	None	None	I
R/F	0.5876	likely_pathogenic	0.6163	pathogenic	-0.224	Destabilizing	0.818	D	0.571	neutral	None	None	None	None	I
R/G	0.2047	likely_benign	0.2223	benign	-0.156	Destabilizing	0.324	N	0.538	neutral	N	0.509894683	None	None	I
R/H	0.1595	likely_benign	0.1658	benign	-0.647	Destabilizing	0.005	N	0.279	neutral	None	None	None	None	I
R/I	0.2495	likely_benign	0.2544	benign	0.453	Stabilizing	0.773	D	0.567	neutral	N	0.510068041	None	None	I
R/K	0.0647	likely_benign	0.0691	benign	-0.097	Destabilizing	0.001	N	0.147	neutral	N	0.419347249	None	None	I
R/L	0.2598	likely_benign	0.2711	benign	0.453	Stabilizing	0.388	N	0.535	neutral	None	None	None	None	I
R/M	0.2538	likely_benign	0.2699	benign	0.009	Stabilizing	0.932	D	0.544	neutral	None	None	None	None	I
R/N	0.4735	ambiguous	0.5307	ambiguous	0.079	Stabilizing	0.388	N	0.475	neutral	None	None	None	None	I
R/P	0.5578	ambiguous	0.5706	pathogenic	0.329	Stabilizing	0.818	D	0.559	neutral	None	None	None	None	I
R/Q	0.1024	likely_benign	0.108	benign	0.003	Stabilizing	0.241	N	0.513	neutral	None	None	None	None	I
R/S	0.3593	ambiguous	0.3877	ambiguous	-0.208	Destabilizing	0.193	N	0.507	neutral	N	0.432201903	None	None	I
R/T	0.2052	likely_benign	0.2233	benign	-0.026	Destabilizing	0.324	N	0.53	neutral	N	0.452809249	None	None	I
R/V	0.3093	likely_benign	0.3204	benign	0.329	Stabilizing	0.69	D	0.554	neutral	None	None	None	None	I
R/W	0.277	likely_benign	0.2909	benign	-0.321	Destabilizing	0.981	D	0.579	neutral	None	None	None	None	I
R/Y	0.4827	ambiguous	0.5199	ambiguous	0.089	Stabilizing	0.69	D	0.568	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.