TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19934	60025;60026;60027	chr2:178592104;178592103;178592102	chr2:179456831;179456830;179456829
N2AB	18293	55102;55103;55104	chr2:178592104;178592103;178592102	chr2:179456831;179456830;179456829
N2A	17366	52321;52322;52323	chr2:178592104;178592103;178592102	chr2:179456831;179456830;179456829
N2B	10869	32830;32831;32832	chr2:178592104;178592103;178592102	chr2:179456831;179456830;179456829
Novex-1	10994	33205;33206;33207	chr2:178592104;178592103;178592102	chr2:179456831;179456830;179456829
Novex-2	11061	33406;33407;33408	chr2:178592104;178592103;178592102	chr2:179456831;179456830;179456829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-32
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.5838
• 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/N	rs1363638353	-0.792	0.642	N	0.425	0.139	0.183819452728	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/N	rs1363638353	-0.792	0.642	N	0.425	0.139	0.183819452728	gnomAD-4.0.0	3.18587E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72014E-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
K/A	0.4231	ambiguous	0.4201	ambiguous	-0.847	Destabilizing	0.495	N	0.463	neutral	None	None	None	None	N
K/C	0.5759	likely_pathogenic	0.5457	ambiguous	-0.802	Destabilizing	0.995	D	0.551	neutral	None	None	None	None	N
K/D	0.7509	likely_pathogenic	0.7748	pathogenic	-0.391	Destabilizing	0.828	D	0.547	neutral	None	None	None	None	N
K/E	0.3529	ambiguous	0.3788	ambiguous	-0.211	Destabilizing	0.425	N	0.451	neutral	N	0.416658369	None	None	N
K/F	0.7928	likely_pathogenic	0.7699	pathogenic	-0.408	Destabilizing	0.893	D	0.587	neutral	None	None	None	None	N
K/G	0.5344	ambiguous	0.5435	ambiguous	-1.228	Destabilizing	0.828	D	0.549	neutral	None	None	None	None	N
K/H	0.332	likely_benign	0.3291	benign	-1.142	Destabilizing	0.007	N	0.419	neutral	None	None	None	None	N
K/I	0.4138	ambiguous	0.4048	ambiguous	0.171	Stabilizing	0.543	D	0.583	neutral	None	None	None	None	N
K/L	0.2961	likely_benign	0.277	benign	0.171	Stabilizing	0.003	N	0.414	neutral	None	None	None	None	N
K/M	0.2215	likely_benign	0.2256	benign	-0.203	Destabilizing	0.863	D	0.566	neutral	N	0.446634559	None	None	N
K/N	0.4559	ambiguous	0.4861	ambiguous	-0.801	Destabilizing	0.642	D	0.425	neutral	N	0.408942963	None	None	N
K/P	0.5614	ambiguous	0.5316	ambiguous	-0.142	Destabilizing	0.981	D	0.607	neutral	None	None	None	None	N
K/Q	0.1656	likely_benign	0.1668	benign	-0.691	Destabilizing	0.642	D	0.418	neutral	N	0.443228895	None	None	N
K/R	0.0852	likely_benign	0.0822	benign	-0.375	Destabilizing	0.001	N	0.256	neutral	N	0.373232879	None	None	N
K/S	0.547	ambiguous	0.5627	ambiguous	-1.41	Destabilizing	0.495	N	0.411	neutral	None	None	None	None	N
K/T	0.1782	likely_benign	0.1998	benign	-1.008	Destabilizing	0.784	D	0.503	neutral	N	0.321742479	None	None	N
K/V	0.3768	ambiguous	0.3597	ambiguous	-0.142	Destabilizing	0.543	D	0.545	neutral	None	None	None	None	N
K/W	0.7927	likely_pathogenic	0.7426	pathogenic	-0.348	Destabilizing	0.995	D	0.567	neutral	None	None	None	None	N
K/Y	0.5927	likely_pathogenic	0.5779	pathogenic	-0.062	Destabilizing	0.893	D	0.636	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.