TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28562	85909;85910;85911	chr2:178560448;178560447;178560446	chr2:179425175;179425174;179425173
N2AB	26921	80986;80987;80988	chr2:178560448;178560447;178560446	chr2:179425175;179425174;179425173
N2A	25994	78205;78206;78207	chr2:178560448;178560447;178560446	chr2:179425175;179425174;179425173
N2B	19497	58714;58715;58716	chr2:178560448;178560447;178560446	chr2:179425175;179425174;179425173
Novex-1	19622	59089;59090;59091	chr2:178560448;178560447;178560446	chr2:179425175;179425174;179425173
Novex-2	19689	59290;59291;59292	chr2:178560448;178560447;178560446	chr2:179425175;179425174;179425173
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-96
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.264
• 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/M	None	None	0.998	N	0.639	0.418	0.504604281553	gnomAD-4.0.0	1.59183E-06	None	None	None	None	N	None	0	0	None	0	2.77824E-05	None	0	0	0	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	0.3128	likely_benign	0.2706	benign	-1.292	Destabilizing	0.994	D	0.439	neutral	N	0.517348225	None	None	N
V/C	0.7642	likely_pathogenic	0.7364	pathogenic	-1.45	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
V/D	0.7966	likely_pathogenic	0.7574	pathogenic	-1.673	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/E	0.6085	likely_pathogenic	0.5543	ambiguous	-1.697	Destabilizing	0.999	D	0.757	deleterious	N	0.512037974	None	None	N
V/F	0.3677	ambiguous	0.306	benign	-1.44	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
V/G	0.475	ambiguous	0.4323	ambiguous	-1.54	Destabilizing	0.999	D	0.792	deleterious	N	0.510596397	None	None	N
V/H	0.7913	likely_pathogenic	0.7481	pathogenic	-1.197	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/I	0.0711	likely_benign	0.0679	benign	-0.717	Destabilizing	0.611	D	0.202	neutral	None	None	None	None	N
V/K	0.5163	ambiguous	0.4924	ambiguous	-0.999	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/L	0.3468	ambiguous	0.2866	benign	-0.717	Destabilizing	0.948	D	0.313	neutral	N	0.472257838	None	None	N
V/M	0.2185	likely_benign	0.1848	benign	-0.676	Destabilizing	0.998	D	0.639	neutral	N	0.510089418	None	None	N
V/N	0.5876	likely_pathogenic	0.5156	ambiguous	-0.946	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/P	0.8413	likely_pathogenic	0.8331	pathogenic	-0.877	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
V/Q	0.5282	ambiguous	0.4723	ambiguous	-1.205	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
V/R	0.4711	ambiguous	0.4519	ambiguous	-0.545	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/S	0.4271	ambiguous	0.3653	ambiguous	-1.409	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
V/T	0.2802	likely_benign	0.2387	benign	-1.329	Destabilizing	0.996	D	0.524	neutral	None	None	None	None	N
V/W	0.9385	likely_pathogenic	0.9228	pathogenic	-1.594	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/Y	0.7675	likely_pathogenic	0.7073	pathogenic	-1.22	Destabilizing	1.0	D	0.754	deleterious	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.