TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21725	65398;65399;65400	chr2:178584378;178584377;178584376	chr2:179449105;179449104;179449103
N2AB	20084	60475;60476;60477	chr2:178584378;178584377;178584376	chr2:179449105;179449104;179449103
N2A	19157	57694;57695;57696	chr2:178584378;178584377;178584376	chr2:179449105;179449104;179449103
N2B	12660	38203;38204;38205	chr2:178584378;178584377;178584376	chr2:179449105;179449104;179449103
Novex-1	12785	38578;38579;38580	chr2:178584378;178584377;178584376	chr2:179449105;179449104;179449103
Novex-2	12852	38779;38780;38781	chr2:178584378;178584377;178584376	chr2:179449105;179449104;179449103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-45
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4029
• 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
V/A	rs543828787	-1.257	0.334	N	0.357	0.223	0.545173277474	gnomAD-2.1.1	1.20937E-04	None	None	None	None	N	None	0	0	None	0	0	None	9.81033E-04	None	0	0	0
V/A	rs543828787	-1.257	0.334	N	0.357	0.223	0.545173277474	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	8.28844E-04	0
V/A	rs543828787	-1.257	0.334	N	0.357	0.223	0.545173277474	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
V/A	rs543828787	-1.257	0.334	N	0.357	0.223	0.545173277474	gnomAD-4.0.0	6.07453E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	9.88598E-04	1.2809E-04
V/I	rs368716894	-0.395	0.002	N	0.104	0.085	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	5.49E-05	0
V/I	rs368716894	-0.395	0.002	N	0.104	0.085	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	7.35E-05	0	0
V/I	rs368716894	-0.395	0.002	N	0.104	0.085	None	gnomAD-4.0.0	7.19086E-05	None	None	None	None	N	None	2.67051E-05	0	None	0	0	None	0	0	8.98701E-05	0	1.28135E-04
V/L	rs368716894	None	0.036	N	0.231	0.05	0.211220785272	gnomAD-4.0.0	3.4221E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49844E-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
V/A	0.2375	likely_benign	0.1845	benign	-0.928	Destabilizing	0.334	N	0.357	neutral	N	0.483078149	None	None	N
V/C	0.7583	likely_pathogenic	0.6736	pathogenic	-0.903	Destabilizing	0.992	D	0.439	neutral	None	None	None	None	N
V/D	0.6356	likely_pathogenic	0.485	ambiguous	-0.411	Destabilizing	0.972	D	0.499	neutral	None	None	None	None	N
V/E	0.468	ambiguous	0.3548	ambiguous	-0.44	Destabilizing	0.963	D	0.464	neutral	N	0.439593944	None	None	N
V/F	0.2636	likely_benign	0.1982	benign	-0.715	Destabilizing	0.85	D	0.418	neutral	None	None	None	None	N
V/G	0.3741	ambiguous	0.3004	benign	-1.177	Destabilizing	0.896	D	0.447	neutral	N	0.474989636	None	None	N
V/H	0.7071	likely_pathogenic	0.5678	pathogenic	-0.492	Destabilizing	0.992	D	0.489	neutral	None	None	None	None	N
V/I	0.0785	likely_benign	0.0712	benign	-0.377	Destabilizing	0.002	N	0.104	neutral	N	0.368216635	None	None	N
V/K	0.5799	likely_pathogenic	0.4376	ambiguous	-0.777	Destabilizing	0.92	D	0.441	neutral	None	None	None	None	N
V/L	0.1722	likely_benign	0.1421	benign	-0.377	Destabilizing	0.036	N	0.231	neutral	N	0.428859662	None	None	N
V/M	0.1402	likely_benign	0.1198	benign	-0.517	Destabilizing	0.059	N	0.215	neutral	None	None	None	None	N
V/N	0.4177	ambiguous	0.3029	benign	-0.642	Destabilizing	0.972	D	0.491	neutral	None	None	None	None	N
V/P	0.7446	likely_pathogenic	0.5768	pathogenic	-0.525	Destabilizing	0.972	D	0.481	neutral	None	None	None	None	N
V/Q	0.4058	ambiguous	0.3164	benign	-0.781	Destabilizing	0.92	D	0.476	neutral	None	None	None	None	N
V/R	0.4857	ambiguous	0.3353	benign	-0.273	Destabilizing	0.92	D	0.493	neutral	None	None	None	None	N
V/S	0.2976	likely_benign	0.2239	benign	-1.154	Destabilizing	0.92	D	0.417	neutral	None	None	None	None	N
V/T	0.1936	likely_benign	0.1516	benign	-1.061	Destabilizing	0.617	D	0.324	neutral	None	None	None	None	N
V/W	0.8456	likely_pathogenic	0.7538	pathogenic	-0.818	Destabilizing	0.992	D	0.552	neutral	None	None	None	None	N
V/Y	0.6781	likely_pathogenic	0.5452	ambiguous	-0.531	Destabilizing	0.92	D	0.449	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.