TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20296	61111;61112;61113	chr2:178590839;178590838;178590837	chr2:179455566;179455565;179455564
N2AB	18655	56188;56189;56190	chr2:178590839;178590838;178590837	chr2:179455566;179455565;179455564
N2A	17728	53407;53408;53409	chr2:178590839;178590838;178590837	chr2:179455566;179455565;179455564
N2B	11231	33916;33917;33918	chr2:178590839;178590838;178590837	chr2:179455566;179455565;179455564
Novex-1	11356	34291;34292;34293	chr2:178590839;178590838;178590837	chr2:179455566;179455565;179455564
Novex-2	11423	34492;34493;34494	chr2:178590839;178590838;178590837	chr2:179455566;179455565;179455564
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-35
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8056
• Predicted PPI site: I

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/Q	rs755102239	0.091	0.966	N	0.414	0.223	0.278968121808	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/Q	rs755102239	0.091	0.966	N	0.414	0.223	0.278968121808	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	rs755102239	0.091	0.966	N	0.414	0.223	0.278968121808	gnomAD-4.0.0	6.57575E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47085E-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	0.1608	likely_benign	0.1496	benign	0.037	Stabilizing	0.688	D	0.444	neutral	None	None	None	None	I
K/C	0.5696	likely_pathogenic	0.5451	ambiguous	-0.301	Destabilizing	0.998	D	0.4	neutral	None	None	None	None	I
K/D	0.2799	likely_benign	0.2735	benign	-0.158	Destabilizing	0.991	D	0.423	neutral	None	None	None	None	I
K/E	0.0914	likely_benign	0.094	benign	-0.173	Destabilizing	0.891	D	0.462	neutral	N	0.39318965	None	None	I
K/F	0.5741	likely_pathogenic	0.5751	pathogenic	-0.294	Destabilizing	0.949	D	0.459	neutral	None	None	None	None	I
K/G	0.2795	likely_benign	0.2699	benign	-0.103	Destabilizing	0.915	D	0.466	neutral	None	None	None	None	I
K/H	0.2534	likely_benign	0.2482	benign	-0.289	Destabilizing	0.998	D	0.409	neutral	None	None	None	None	I
K/I	0.1919	likely_benign	0.1843	benign	0.32	Stabilizing	0.669	D	0.508	neutral	N	0.422360551	None	None	I
K/L	0.1887	likely_benign	0.1858	benign	0.32	Stabilizing	0.007	N	0.237	neutral	None	None	None	None	I
K/M	0.155	likely_benign	0.1516	benign	0.058	Stabilizing	0.325	N	0.327	neutral	None	None	None	None	I
K/N	0.2387	likely_benign	0.2425	benign	0.153	Stabilizing	0.989	D	0.391	neutral	N	0.452470027	None	None	I
K/P	0.3369	likely_benign	0.3131	benign	0.25	Stabilizing	0.991	D	0.435	neutral	None	None	None	None	I
K/Q	0.1057	likely_benign	0.1036	benign	-0.016	Destabilizing	0.966	D	0.414	neutral	N	0.450949875	None	None	I
K/R	0.0828	likely_benign	0.0857	benign	-0.049	Destabilizing	0.891	D	0.442	neutral	N	0.443791829	None	None	I
K/S	0.2105	likely_benign	0.2027	benign	-0.244	Destabilizing	0.915	D	0.431	neutral	None	None	None	None	I
K/T	0.1015	likely_benign	0.0981	benign	-0.136	Destabilizing	0.801	D	0.487	neutral	N	0.424224633	None	None	I
K/V	0.1598	likely_benign	0.1479	benign	0.25	Stabilizing	0.525	D	0.421	neutral	None	None	None	None	I
K/W	0.6806	likely_pathogenic	0.6792	pathogenic	-0.372	Destabilizing	0.998	D	0.422	neutral	None	None	None	None	I
K/Y	0.4713	ambiguous	0.4661	ambiguous	-0.012	Destabilizing	0.974	D	0.457	neutral	None	None	None	None	I

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.