TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27870	83833;83834;83835	chr2:178562524;178562523;178562522	chr2:179427251;179427250;179427249
N2AB	26229	78910;78911;78912	chr2:178562524;178562523;178562522	chr2:179427251;179427250;179427249
N2A	25302	76129;76130;76131	chr2:178562524;178562523;178562522	chr2:179427251;179427250;179427249
N2B	18805	56638;56639;56640	chr2:178562524;178562523;178562522	chr2:179427251;179427250;179427249
Novex-1	18930	57013;57014;57015	chr2:178562524;178562523;178562522	chr2:179427251;179427250;179427249
Novex-2	18997	57214;57215;57216	chr2:178562524;178562523;178562522	chr2:179427251;179427250;179427249
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-91
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1618
• 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
V/G	None	None	0.999	N	0.831	0.582	0.791155293085	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
V/I	rs772190104	-0.08	0.37	N	0.23	0.105	0.408036853922	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	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
V/A	0.8008	likely_pathogenic	0.8393	pathogenic	-1.954	Destabilizing	0.978	D	0.669	neutral	N	0.479098374	None	None	N
V/C	0.9313	likely_pathogenic	0.9428	pathogenic	-1.474	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
V/D	0.9871	likely_pathogenic	0.9917	pathogenic	-2.624	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
V/E	0.9706	likely_pathogenic	0.9807	pathogenic	-2.429	Highly Destabilizing	0.999	D	0.805	deleterious	N	0.521143008	None	None	N
V/F	0.6771	likely_pathogenic	0.7622	pathogenic	-1.141	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
V/G	0.8111	likely_pathogenic	0.846	pathogenic	-2.463	Highly Destabilizing	0.999	D	0.831	deleterious	N	0.51105415	None	None	N
V/H	0.9919	likely_pathogenic	0.9952	pathogenic	-2.289	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/I	0.0902	likely_benign	0.0912	benign	-0.546	Destabilizing	0.37	N	0.23	neutral	N	0.444063975	None	None	N
V/K	0.982	likely_pathogenic	0.988	pathogenic	-1.675	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
V/L	0.3941	ambiguous	0.4731	ambiguous	-0.546	Destabilizing	0.9	D	0.643	neutral	N	0.443842183	None	None	N
V/M	0.4679	ambiguous	0.5503	ambiguous	-0.602	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
V/N	0.9573	likely_pathogenic	0.9705	pathogenic	-1.932	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
V/P	0.9505	likely_pathogenic	0.9702	pathogenic	-0.988	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/Q	0.9721	likely_pathogenic	0.9819	pathogenic	-1.804	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
V/R	0.9773	likely_pathogenic	0.9838	pathogenic	-1.487	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
V/S	0.9311	likely_pathogenic	0.9495	pathogenic	-2.501	Highly Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
V/T	0.8748	likely_pathogenic	0.894	pathogenic	-2.175	Highly Destabilizing	0.992	D	0.762	deleterious	None	None	None	None	N
V/W	0.9904	likely_pathogenic	0.9948	pathogenic	-1.7	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/Y	0.961	likely_pathogenic	0.9773	pathogenic	-1.301	Destabilizing	0.999	D	0.779	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.