TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3063	9412;9413;9414	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857
N2AB	3063	9412;9413;9414	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857
N2A	3063	9412;9413;9414	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857
N2B	3017	9274;9275;9276	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857
Novex-1	3017	9274;9275;9276	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857
Novex-2	3017	9274;9275;9276	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857
Novex-3	3063	9412;9413;9414	chr2:178768132;178768131;178768130	chr2:179632859;179632858;179632857

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-21
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4257
• 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
H/D	rs1325663861	None	0.959	N	0.53	0.502	0.292062946507	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
H/D	rs1325663861	None	0.959	N	0.53	0.502	0.292062946507	gnomAD-4.0.0	6.57652E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	0	0
H/R	rs762023362	-0.619	0.828	N	0.446	0.489	0.235664433957	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
H/R	rs762023362	-0.619	0.828	N	0.446	0.489	0.235664433957	gnomAD-4.0.0	2.73642E-06	None	None	None	None	N	None	0	2.23654E-05	None	0	0	None	0	0	2.6979E-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
H/A	0.7231	likely_pathogenic	0.6478	pathogenic	-0.516	Destabilizing	0.927	D	0.487	neutral	None	None	None	None	N
H/C	0.6941	likely_pathogenic	0.6241	pathogenic	0.234	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	N
H/D	0.622	likely_pathogenic	0.5596	ambiguous	-0.101	Destabilizing	0.959	D	0.53	neutral	N	0.485117775	None	None	N
H/E	0.7717	likely_pathogenic	0.7037	pathogenic	-0.01	Destabilizing	0.864	D	0.356	neutral	None	None	None	None	N
H/F	0.7524	likely_pathogenic	0.6875	pathogenic	0.694	Stabilizing	0.999	D	0.599	neutral	None	None	None	None	N
H/G	0.7344	likely_pathogenic	0.6494	pathogenic	-0.875	Destabilizing	0.984	D	0.561	neutral	None	None	None	None	N
H/I	0.8892	likely_pathogenic	0.8522	pathogenic	0.46	Stabilizing	0.999	D	0.627	neutral	None	None	None	None	N
H/K	0.6474	likely_pathogenic	0.5694	pathogenic	-0.24	Destabilizing	0.148	N	0.223	neutral	None	None	None	None	N
H/L	0.4908	ambiguous	0.4085	ambiguous	0.46	Stabilizing	0.979	D	0.588	neutral	N	0.499719629	None	None	N
H/M	0.8476	likely_pathogenic	0.8126	pathogenic	0.247	Stabilizing	0.999	D	0.599	neutral	None	None	None	None	N
H/N	0.2677	likely_benign	0.2409	benign	-0.359	Destabilizing	0.979	D	0.46	neutral	N	0.499174197	None	None	N
H/P	0.2244	likely_benign	0.1824	benign	0.157	Stabilizing	0.993	D	0.605	neutral	N	0.421326116	None	None	N
H/Q	0.5952	likely_pathogenic	0.5034	ambiguous	-0.153	Destabilizing	0.476	N	0.173	neutral	N	0.469658452	None	None	N
H/R	0.456	ambiguous	0.3603	ambiguous	-0.718	Destabilizing	0.828	D	0.446	neutral	N	0.455966152	None	None	N
H/S	0.6424	likely_pathogenic	0.5749	pathogenic	-0.438	Destabilizing	0.927	D	0.518	neutral	None	None	None	None	N
H/T	0.7419	likely_pathogenic	0.7031	pathogenic	-0.237	Destabilizing	0.984	D	0.568	neutral	None	None	None	None	N
H/V	0.8298	likely_pathogenic	0.7807	pathogenic	0.157	Stabilizing	0.984	D	0.608	neutral	None	None	None	None	N
H/W	0.8547	likely_pathogenic	0.8062	pathogenic	1.012	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
H/Y	0.3843	ambiguous	0.3024	benign	1.092	Stabilizing	0.993	D	0.47	neutral	D	0.575434902	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.