TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25098	75517;75518;75519	chr2:178570840;178570839;178570838	chr2:179435567;179435566;179435565
N2AB	23457	70594;70595;70596	chr2:178570840;178570839;178570838	chr2:179435567;179435566;179435565
N2A	22530	67813;67814;67815	chr2:178570840;178570839;178570838	chr2:179435567;179435566;179435565
N2B	16033	48322;48323;48324	chr2:178570840;178570839;178570838	chr2:179435567;179435566;179435565
Novex-1	16158	48697;48698;48699	chr2:178570840;178570839;178570838	chr2:179435567;179435566;179435565
Novex-2	16225	48898;48899;48900	chr2:178570840;178570839;178570838	chr2:179435567;179435566;179435565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-70
• Domain position: 93
• Structural Position: 125
• Q(SASA): 0.3472
• 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
G/R	rs747022529	0.114	0.995	N	0.881	0.348	0.197625483188	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	8.7E-05	None	0	0	None	0	None	0	1.78E-05	0
G/R	rs747022529	0.114	0.995	N	0.881	0.348	0.197625483188	gnomAD-4.0.0	9.55052E-06	None	None	None	None	N	None	0	6.86028E-05	None	0	0	None	0	0	8.5777E-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
G/A	0.3565	ambiguous	0.3055	benign	-0.426	Destabilizing	0.981	D	0.663	prob.neutral	N	0.497782951	None	None	N
G/C	0.6307	likely_pathogenic	0.5585	ambiguous	-0.914	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/D	0.6024	likely_pathogenic	0.5089	ambiguous	-0.31	Destabilizing	0.992	D	0.769	deleterious	None	None	None	None	N
G/E	0.6059	likely_pathogenic	0.4948	ambiguous	-0.424	Destabilizing	0.465	N	0.676	prob.neutral	N	0.437195852	None	None	N
G/F	0.9178	likely_pathogenic	0.8931	pathogenic	-0.886	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
G/H	0.8459	likely_pathogenic	0.7981	pathogenic	-0.74	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
G/I	0.8416	likely_pathogenic	0.786	pathogenic	-0.308	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
G/K	0.8191	likely_pathogenic	0.7585	pathogenic	-0.861	Destabilizing	0.992	D	0.849	deleterious	None	None	None	None	N
G/L	0.8404	likely_pathogenic	0.786	pathogenic	-0.308	Destabilizing	0.996	D	0.876	deleterious	None	None	None	None	N
G/M	0.8599	likely_pathogenic	0.8105	pathogenic	-0.385	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
G/N	0.7116	likely_pathogenic	0.648	pathogenic	-0.548	Destabilizing	0.996	D	0.751	deleterious	None	None	None	None	N
G/P	0.9296	likely_pathogenic	0.928	pathogenic	-0.308	Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
G/Q	0.728	likely_pathogenic	0.6606	pathogenic	-0.76	Destabilizing	0.992	D	0.883	deleterious	None	None	None	None	N
G/R	0.7009	likely_pathogenic	0.6293	pathogenic	-0.519	Destabilizing	0.995	D	0.881	deleterious	N	0.447761941	None	None	N
G/S	0.2808	likely_benign	0.2316	benign	-0.836	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
G/T	0.5367	ambiguous	0.4655	ambiguous	-0.859	Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
G/V	0.6912	likely_pathogenic	0.6135	pathogenic	-0.308	Destabilizing	0.997	D	0.874	deleterious	N	0.493318493	None	None	N
G/W	0.8597	likely_pathogenic	0.8235	pathogenic	-1.103	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/Y	0.8711	likely_pathogenic	0.8275	pathogenic	-0.716	Destabilizing	1.0	D	0.895	deleterious	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.