TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29080	87463;87464;87465	chr2:178558116;178558115;178558114	chr2:179422843;179422842;179422841
N2AB	27439	82540;82541;82542	chr2:178558116;178558115;178558114	chr2:179422843;179422842;179422841
N2A	26512	79759;79760;79761	chr2:178558116;178558115;178558114	chr2:179422843;179422842;179422841
N2B	20015	60268;60269;60270	chr2:178558116;178558115;178558114	chr2:179422843;179422842;179422841
Novex-1	20140	60643;60644;60645	chr2:178558116;178558115;178558114	chr2:179422843;179422842;179422841
Novex-2	20207	60844;60845;60846	chr2:178558116;178558115;178558114	chr2:179422843;179422842;179422841
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-145
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2288
• 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
R/G	rs760115899	-2.444	0.324	N	0.528	0.34	0.326074293725	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/G	rs760115899	-2.444	0.324	N	0.528	0.34	0.326074293725	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85788E-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
R/A	0.4867	ambiguous	0.4996	ambiguous	-0.877	Destabilizing	0.116	N	0.517	neutral	None	None	None	None	N
R/C	0.2145	likely_benign	0.2086	benign	-0.833	Destabilizing	0.981	D	0.646	neutral	None	None	None	None	N
R/D	0.8484	likely_pathogenic	0.8611	pathogenic	0.104	Stabilizing	0.388	N	0.59	neutral	None	None	None	None	N
R/E	0.459	ambiguous	0.48	ambiguous	0.236	Stabilizing	0.116	N	0.534	neutral	None	None	None	None	N
R/F	0.6032	likely_pathogenic	0.5991	pathogenic	-0.796	Destabilizing	0.932	D	0.635	neutral	None	None	None	None	N
R/G	0.4077	ambiguous	0.4625	ambiguous	-1.171	Destabilizing	0.324	N	0.528	neutral	N	0.503695777	None	None	N
R/H	0.152	likely_benign	0.1541	benign	-1.543	Destabilizing	0.818	D	0.519	neutral	None	None	None	None	N
R/I	0.2994	likely_benign	0.3005	benign	-0.091	Destabilizing	0.773	D	0.624	neutral	N	0.484416582	None	None	N
R/K	0.0725	likely_benign	0.0751	benign	-0.631	Destabilizing	None	N	0.155	neutral	N	0.332951189	None	None	N
R/L	0.2921	likely_benign	0.2851	benign	-0.091	Destabilizing	0.388	N	0.528	neutral	None	None	None	None	N
R/M	0.2881	likely_benign	0.2948	benign	-0.459	Destabilizing	0.932	D	0.59	neutral	None	None	None	None	N
R/N	0.713	likely_pathogenic	0.7282	pathogenic	-0.241	Destabilizing	0.388	N	0.517	neutral	None	None	None	None	N
R/P	0.9104	likely_pathogenic	0.9244	pathogenic	-0.333	Destabilizing	0.818	D	0.611	neutral	None	None	None	None	N
R/Q	0.1232	likely_benign	0.1263	benign	-0.369	Destabilizing	0.241	N	0.543	neutral	None	None	None	None	N
R/S	0.6174	likely_pathogenic	0.6547	pathogenic	-1.057	Destabilizing	0.193	N	0.507	neutral	N	0.503522418	None	None	N
R/T	0.3699	ambiguous	0.3923	ambiguous	-0.733	Destabilizing	0.324	N	0.523	neutral	N	0.503522418	None	None	N
R/V	0.3778	ambiguous	0.3748	ambiguous	-0.333	Destabilizing	0.69	D	0.606	neutral	None	None	None	None	N
R/W	0.2473	likely_benign	0.2493	benign	-0.496	Destabilizing	0.981	D	0.665	neutral	None	None	None	None	N
R/Y	0.4927	ambiguous	0.4798	ambiguous	-0.195	Destabilizing	0.932	D	0.611	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.