TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19345	58258;58259;58260	chr2:178594461;178594460;178594459	chr2:179459188;179459187;179459186
N2AB	17704	53335;53336;53337	chr2:178594461;178594460;178594459	chr2:179459188;179459187;179459186
N2A	16777	50554;50555;50556	chr2:178594461;178594460;178594459	chr2:179459188;179459187;179459186
N2B	10280	31063;31064;31065	chr2:178594461;178594460;178594459	chr2:179459188;179459187;179459186
Novex-1	10405	31438;31439;31440	chr2:178594461;178594460;178594459	chr2:179459188;179459187;179459186
Novex-2	10472	31639;31640;31641	chr2:178594461;178594460;178594459	chr2:179459188;179459187;179459186
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-28
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.1933
• 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/A	rs567680958	-0.875	0.726	N	0.52	0.406	0.266843984389	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.9431E-04	None	0	0	0
T/A	rs567680958	-0.875	0.726	N	0.52	0.406	0.266843984389	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
T/A	rs567680958	-0.875	0.726	N	0.52	0.406	0.266843984389	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
T/A	rs567680958	-0.875	0.726	N	0.52	0.406	0.266843984389	gnomAD-4.0.0	1.17765E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.08672E-04	0
T/I	rs551040385	0.3	0.989	N	0.719	0.489	0.533276065955	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/I	rs551040385	0.3	0.989	N	0.719	0.489	0.533276065955	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs551040385	0.3	0.989	N	0.719	0.489	0.533276065955	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
T/I	rs551040385	0.3	0.989	N	0.719	0.489	0.533276065955	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	2.40732E-05	0	None	0	0	None	0	0	0	0	0
T/N	rs551040385	None	0.957	N	0.596	0.453	0.448300063881	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
T/A	0.1219	likely_benign	0.1131	benign	-0.805	Destabilizing	0.726	D	0.52	neutral	N	0.487758882	None	None	N
T/C	0.4487	ambiguous	0.4323	ambiguous	-0.516	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
T/D	0.4989	ambiguous	0.4625	ambiguous	-0.084	Destabilizing	0.983	D	0.653	neutral	None	None	None	None	N
T/E	0.3139	likely_benign	0.2879	benign	-0.05	Destabilizing	0.983	D	0.641	neutral	None	None	None	None	N
T/F	0.4493	ambiguous	0.4111	ambiguous	-0.795	Destabilizing	0.992	D	0.8	deleterious	None	None	None	None	N
T/G	0.4675	ambiguous	0.4463	ambiguous	-1.094	Destabilizing	0.895	D	0.631	neutral	None	None	None	None	N
T/H	0.3746	ambiguous	0.3369	benign	-1.322	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
T/I	0.165	likely_benign	0.154	benign	-0.119	Destabilizing	0.989	D	0.719	prob.delet.	N	0.497126951	None	None	N
T/K	0.3193	likely_benign	0.2723	benign	-0.673	Destabilizing	0.968	D	0.65	neutral	None	None	None	None	N
T/L	0.1751	likely_benign	0.16	benign	-0.119	Destabilizing	0.944	D	0.583	neutral	None	None	None	None	N
T/M	0.1218	likely_benign	0.1107	benign	0.02	Stabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
T/N	0.2157	likely_benign	0.2018	benign	-0.712	Destabilizing	0.957	D	0.596	neutral	N	0.487251903	None	None	N
T/P	0.3653	ambiguous	0.3201	benign	-0.314	Destabilizing	0.989	D	0.722	prob.delet.	N	0.479556128	None	None	N
T/Q	0.2784	likely_benign	0.257	benign	-0.768	Destabilizing	0.983	D	0.736	prob.delet.	None	None	None	None	N
T/R	0.3063	likely_benign	0.2474	benign	-0.535	Destabilizing	0.983	D	0.723	prob.delet.	None	None	None	None	N
T/S	0.1558	likely_benign	0.1496	benign	-1.008	Destabilizing	0.146	N	0.391	neutral	N	0.487251903	None	None	N
T/V	0.1199	likely_benign	0.1166	benign	-0.314	Destabilizing	0.944	D	0.507	neutral	None	None	None	None	N
T/W	0.8076	likely_pathogenic	0.775	pathogenic	-0.765	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
T/Y	0.5078	ambiguous	0.4612	ambiguous	-0.513	Destabilizing	0.997	D	0.8	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.