TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30812	92659;92660;92661	chr2:178549192;178549191;178549190	chr2:179413919;179413918;179413917
N2AB	29171	87736;87737;87738	chr2:178549192;178549191;178549190	chr2:179413919;179413918;179413917
N2A	28244	84955;84956;84957	chr2:178549192;178549191;178549190	chr2:179413919;179413918;179413917
N2B	21747	65464;65465;65466	chr2:178549192;178549191;178549190	chr2:179413919;179413918;179413917
Novex-1	21872	65839;65840;65841	chr2:178549192;178549191;178549190	chr2:179413919;179413918;179413917
Novex-2	21939	66040;66041;66042	chr2:178549192;178549191;178549190	chr2:179413919;179413918;179413917
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-112
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.1916
• 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
L/F	rs776239659	-1.217	0.992	N	0.747	0.17	0.445007932271	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
L/F	rs776239659	-1.217	0.992	N	0.747	0.17	0.445007932271	gnomAD-4.0.0	3.18262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71582E-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	0.3087	likely_benign	0.276	benign	-1.204	Destabilizing	0.797	D	0.653	prob.neutral	None	None	None	None	N
L/C	0.5392	ambiguous	0.4975	ambiguous	-0.659	Destabilizing	0.998	D	0.707	prob.delet.	None	None	None	None	N
L/D	0.8105	likely_pathogenic	0.7742	pathogenic	-0.639	Destabilizing	0.965	D	0.825	deleterious	None	None	None	None	N
L/E	0.5429	ambiguous	0.4945	ambiguous	-0.695	Destabilizing	0.965	D	0.813	deleterious	None	None	None	None	N
L/F	0.175	likely_benign	0.1506	benign	-0.94	Destabilizing	0.992	D	0.747	deleterious	N	0.469663348	None	None	N
L/G	0.5625	ambiguous	0.5289	ambiguous	-1.447	Destabilizing	0.965	D	0.819	deleterious	None	None	None	None	N
L/H	0.3161	likely_benign	0.268	benign	-0.592	Destabilizing	0.998	D	0.878	deleterious	N	0.472783798	None	None	N
L/I	0.1533	likely_benign	0.1293	benign	-0.65	Destabilizing	0.923	D	0.642	neutral	N	0.463969526	None	None	N
L/K	0.4116	ambiguous	0.3662	ambiguous	-0.754	Destabilizing	0.965	D	0.801	deleterious	None	None	None	None	N
L/M	0.1366	likely_benign	0.1286	benign	-0.499	Destabilizing	0.994	D	0.709	prob.delet.	None	None	None	None	N
L/N	0.4452	ambiguous	0.4081	ambiguous	-0.49	Destabilizing	0.982	D	0.853	deleterious	None	None	None	None	N
L/P	0.1818	likely_benign	0.1392	benign	-0.802	Destabilizing	0.041	N	0.695	prob.delet.	N	0.446770632	None	None	N
L/Q	0.2145	likely_benign	0.1798	benign	-0.731	Destabilizing	0.982	D	0.843	deleterious	None	None	None	None	N
L/R	0.3125	likely_benign	0.2787	benign	-0.093	Destabilizing	0.977	D	0.824	deleterious	N	0.464301212	None	None	N
L/S	0.4029	ambiguous	0.3607	ambiguous	-1.013	Destabilizing	0.965	D	0.802	deleterious	None	None	None	None	N
L/T	0.3385	likely_benign	0.2899	benign	-0.961	Destabilizing	0.965	D	0.733	deleterious	None	None	None	None	N
L/V	0.144	likely_benign	0.1227	benign	-0.802	Destabilizing	0.856	D	0.619	neutral	N	0.484227368	None	None	N
L/W	0.3101	likely_benign	0.2791	benign	-0.948	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
L/Y	0.3655	ambiguous	0.3311	benign	-0.739	Destabilizing	0.994	D	0.751	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.