TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2983	9172;9173;9174	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614
N2AB	2983	9172;9173;9174	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614
N2A	2983	9172;9173;9174	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614
N2B	2937	9034;9035;9036	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614
Novex-1	2937	9034;9035;9036	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614
Novex-2	2937	9034;9035;9036	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614
Novex-3	2983	9172;9173;9174	chr2:178768889;178768888;178768887	chr2:179633616;179633615;179633614

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-20
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.5459
• 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
K/R	rs1387550627	None	0.217	N	0.368	0.195	0.264547087235	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1387550627	None	0.217	N	0.368	0.195	0.264547087235	gnomAD-4.0.0	6.56909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46959E-05	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
K/A	0.9541	likely_pathogenic	0.9358	pathogenic	0.078	Stabilizing	0.996	D	0.609	neutral	None	None	None	None	N
K/C	0.9819	likely_pathogenic	0.9774	pathogenic	-0.007	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/D	0.9645	likely_pathogenic	0.9505	pathogenic	-0.031	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/E	0.8954	likely_pathogenic	0.8485	pathogenic	-0.029	Destabilizing	0.989	D	0.581	neutral	N	0.506333618	None	None	N
K/F	0.9896	likely_pathogenic	0.9877	pathogenic	-0.103	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/G	0.799	likely_pathogenic	0.7676	pathogenic	-0.13	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	N
K/H	0.7858	likely_pathogenic	0.767	pathogenic	-0.429	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
K/I	0.9874	likely_pathogenic	0.9777	pathogenic	0.552	Stabilizing	0.999	D	0.647	neutral	D	0.585113543	None	None	N
K/L	0.9241	likely_pathogenic	0.9077	pathogenic	0.552	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	N
K/M	0.8453	likely_pathogenic	0.8104	pathogenic	0.378	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	N
K/N	0.8819	likely_pathogenic	0.85	pathogenic	0.371	Stabilizing	0.998	D	0.621	neutral	N	0.508096287	None	None	N
K/P	0.9966	likely_pathogenic	0.994	pathogenic	0.422	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/Q	0.6729	likely_pathogenic	0.6362	pathogenic	0.168	Stabilizing	0.997	D	0.63	neutral	D	0.539891177	None	None	N
K/R	0.1919	likely_benign	0.188	benign	0.043	Stabilizing	0.217	N	0.368	neutral	N	0.487852958	None	None	N
K/S	0.9543	likely_pathogenic	0.9389	pathogenic	-0.083	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	N
K/T	0.8936	likely_pathogenic	0.852	pathogenic	0.062	Stabilizing	0.998	D	0.607	neutral	N	0.507974338	None	None	N
K/V	0.9771	likely_pathogenic	0.9631	pathogenic	0.422	Stabilizing	0.999	D	0.599	neutral	None	None	None	None	N
K/W	0.9811	likely_pathogenic	0.9783	pathogenic	-0.121	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/Y	0.9583	likely_pathogenic	0.9507	pathogenic	0.228	Stabilizing	1.0	D	0.622	neutral	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.