TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32402	97429;97430;97431	chr2:178542552;178542551;178542550	chr2:179407279;179407278;179407277
N2AB	30761	92506;92507;92508	chr2:178542552;178542551;178542550	chr2:179407279;179407278;179407277
N2A	29834	89725;89726;89727	chr2:178542552;178542551;178542550	chr2:179407279;179407278;179407277
N2B	23337	70234;70235;70236	chr2:178542552;178542551;178542550	chr2:179407279;179407278;179407277
Novex-1	23462	70609;70610;70611	chr2:178542552;178542551;178542550	chr2:179407279;179407278;179407277
Novex-2	23529	70810;70811;70812	chr2:178542552;178542551;178542550	chr2:179407279;179407278;179407277
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-124
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2936
• 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
P/L	None	None	0.704	N	0.685	0.36	0.424549175451	gnomAD-4.0.0	6.89587E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.17195E-05	0
P/R	rs761156054	-0.456	0.996	N	0.73	0.368	None	gnomAD-2.1.1	2.18E-05	None	None	None	None	I	None	0	2.86E-05	None	0	0	None	3.38E-05	None	0	3.18E-05	0
P/R	rs761156054	-0.456	0.996	N	0.73	0.368	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
P/R	rs761156054	-0.456	0.996	N	0.73	0.368	None	gnomAD-4.0.0	1.68515E-05	None	None	None	None	I	None	0	1.67802E-05	None	0	0	None	0	4.97347E-04	1.62169E-05	2.21852E-05	3.23217E-05
P/S	rs764632520	-1.441	0.959	N	0.697	0.338	0.250039746154	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
P/S	rs764632520	-1.441	0.959	N	0.697	0.338	0.250039746154	gnomAD-4.0.0	2.0691E-06	None	None	None	None	I	None	3.01386E-05	0	None	0	0	None	0	0	1.81261E-06	0	0
P/T	rs764632520	-1.398	0.92	N	0.683	0.313	None	gnomAD-2.1.1	2.18E-05	None	None	None	None	I	None	0	2.86E-05	None	0	0	None	3.38E-05	None	0	3.18E-05	0
P/T	rs764632520	-1.398	0.92	N	0.683	0.313	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
P/T	rs764632520	-1.398	0.92	N	0.683	0.313	None	gnomAD-4.0.0	1.68537E-05	None	None	None	None	I	None	0	1.67791E-05	None	0	0	None	0	4.97183E-04	1.622E-05	2.21921E-05	3.23206E-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
P/A	0.1062	likely_benign	0.0895	benign	-1.409	Destabilizing	0.826	D	0.68	prob.neutral	N	0.497631022	None	None	I
P/C	0.5263	ambiguous	0.4254	ambiguous	-1.058	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
P/D	0.7504	likely_pathogenic	0.6808	pathogenic	-1.562	Destabilizing	0.997	D	0.681	prob.neutral	None	None	None	None	I
P/E	0.3747	ambiguous	0.3128	benign	-1.619	Destabilizing	0.997	D	0.688	prob.neutral	None	None	None	None	I
P/F	0.5507	ambiguous	0.4317	ambiguous	-1.413	Destabilizing	0.991	D	0.762	deleterious	None	None	None	None	I
P/G	0.5651	likely_pathogenic	0.475	ambiguous	-1.649	Destabilizing	0.99	D	0.739	prob.delet.	None	None	None	None	I
P/H	0.3545	ambiguous	0.2721	benign	-1.14	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	I
P/I	0.2159	likely_benign	0.1621	benign	-0.868	Destabilizing	0.17	N	0.583	neutral	None	None	None	None	I
P/K	0.3613	ambiguous	0.2877	benign	-1.036	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	I
P/L	0.153	likely_benign	0.1129	benign	-0.868	Destabilizing	0.704	D	0.685	prob.neutral	N	0.512059249	None	None	I
P/M	0.2934	likely_benign	0.2247	benign	-0.615	Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	I
P/N	0.5669	likely_pathogenic	0.473	ambiguous	-0.835	Destabilizing	0.997	D	0.731	prob.delet.	None	None	None	None	I
P/Q	0.2153	likely_benign	0.1622	benign	-1.144	Destabilizing	0.996	D	0.669	neutral	N	0.506071768	None	None	I
P/R	0.2931	likely_benign	0.2151	benign	-0.441	Destabilizing	0.996	D	0.73	prob.delet.	N	0.512819717	None	None	I
P/S	0.2311	likely_benign	0.1844	benign	-1.274	Destabilizing	0.959	D	0.697	prob.neutral	N	0.487371628	None	None	I
P/T	0.1746	likely_benign	0.137	benign	-1.236	Destabilizing	0.92	D	0.683	prob.neutral	N	0.480383416	None	None	I
P/V	0.1775	likely_benign	0.1346	benign	-1.015	Destabilizing	0.079	N	0.503	neutral	None	None	None	None	I
P/W	0.8124	likely_pathogenic	0.7086	pathogenic	-1.504	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
P/Y	0.5779	likely_pathogenic	0.4701	ambiguous	-1.207	Destabilizing	0.997	D	0.771	deleterious	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.