TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18627	56104;56105;56106	chr2:178601025;178601024;178601023	chr2:179465752;179465751;179465750
N2AB	16986	51181;51182;51183	chr2:178601025;178601024;178601023	chr2:179465752;179465751;179465750
N2A	16059	48400;48401;48402	chr2:178601025;178601024;178601023	chr2:179465752;179465751;179465750
N2B	9562	28909;28910;28911	chr2:178601025;178601024;178601023	chr2:179465752;179465751;179465750
Novex-1	9687	29284;29285;29286	chr2:178601025;178601024;178601023	chr2:179465752;179465751;179465750
Novex-2	9754	29485;29486;29487	chr2:178601025;178601024;178601023	chr2:179465752;179465751;179465750
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: Fn3-23
• Domain position: 49
• Structural Position: 54
• Q(SASA): 0.5819
• 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/T	rs727503597	None	0.001	N	0.093	0.181	0.247872288689	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs727503597	None	0.001	N	0.093	0.181	0.247872288689	gnomAD-4.0.0	1.42123E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.56654E-05	0	3.40321E-05

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	0.2786	likely_benign	0.2032	benign	0.013	Stabilizing	0.061	N	0.155	neutral	None	None	None	None	N
K/C	0.6773	likely_pathogenic	0.5444	ambiguous	-0.166	Destabilizing	0.983	D	0.183	neutral	None	None	None	None	N
K/D	0.5846	likely_pathogenic	0.4378	ambiguous	0.073	Stabilizing	0.001	N	0.085	neutral	None	None	None	None	N
K/E	0.1482	likely_benign	0.1137	benign	0.062	Stabilizing	0.001	N	0.045	neutral	N	0.388223761	None	None	N
K/F	0.8143	likely_pathogenic	0.6667	pathogenic	-0.312	Destabilizing	0.836	D	0.269	neutral	None	None	None	None	N
K/G	0.3698	ambiguous	0.2543	benign	-0.154	Destabilizing	0.001	N	0.094	neutral	None	None	None	None	N
K/H	0.3883	ambiguous	0.2897	benign	-0.468	Destabilizing	0.836	D	0.171	neutral	None	None	None	None	N
K/I	0.3561	ambiguous	0.2611	benign	0.367	Stabilizing	0.264	N	0.293	neutral	None	None	None	None	N
K/L	0.3485	ambiguous	0.2604	benign	0.367	Stabilizing	0.129	N	0.175	neutral	None	None	None	None	N
K/M	0.2544	likely_benign	0.1983	benign	0.271	Stabilizing	0.794	D	0.171	neutral	N	0.508419311	None	None	N
K/N	0.4246	ambiguous	0.2958	benign	0.292	Stabilizing	0.183	N	0.108	neutral	N	0.414815716	None	None	N
K/P	0.4058	ambiguous	0.3838	ambiguous	0.276	Stabilizing	0.593	D	0.251	neutral	None	None	None	None	N
K/Q	0.1108	likely_benign	0.0892	benign	0.083	Stabilizing	0.021	N	0.099	neutral	N	0.410159258	None	None	N
K/R	0.0874	likely_benign	0.0771	benign	0.042	Stabilizing	0.183	N	0.145	neutral	N	0.443733114	None	None	N
K/S	0.3879	ambiguous	0.2647	benign	-0.192	Destabilizing	0.129	N	0.129	neutral	None	None	None	None	N
K/T	0.1968	likely_benign	0.1415	benign	-0.065	Destabilizing	0.001	N	0.093	neutral	N	0.451179161	None	None	N
K/V	0.2849	likely_benign	0.2063	benign	0.276	Stabilizing	0.001	N	0.117	neutral	None	None	None	None	N
K/W	0.807	likely_pathogenic	0.6883	pathogenic	-0.334	Destabilizing	0.983	D	0.185	neutral	None	None	None	None	N
K/Y	0.6805	likely_pathogenic	0.5414	ambiguous	0.04	Stabilizing	0.836	D	0.272	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.