TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31204	93835;93836;93837	chr2:178548016;178548015;178548014	chr2:179412743;179412742;179412741
N2AB	29563	88912;88913;88914	chr2:178548016;178548015;178548014	chr2:179412743;179412742;179412741
N2A	28636	86131;86132;86133	chr2:178548016;178548015;178548014	chr2:179412743;179412742;179412741
N2B	22139	66640;66641;66642	chr2:178548016;178548015;178548014	chr2:179412743;179412742;179412741
Novex-1	22264	67015;67016;67017	chr2:178548016;178548015;178548014	chr2:179412743;179412742;179412741
Novex-2	22331	67216;67217;67218	chr2:178548016;178548015;178548014	chr2:179412743;179412742;179412741
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-115
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.185
• 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/I	rs750367979	0.533	0.994	N	0.592	0.199	0.548443230319	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
V/I	rs750367979	0.533	0.994	N	0.592	0.199	0.548443230319	gnomAD-4.0.0	3.18249E-06	None	None	None	None	N	None	0	4.57373E-05	None	0	0	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	0.4786	ambiguous	0.5431	ambiguous	-1.456	Destabilizing	0.997	D	0.655	prob.neutral	N	0.486164449	None	None	N
V/C	0.8797	likely_pathogenic	0.9143	pathogenic	-1.139	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/D	0.9311	likely_pathogenic	0.9491	pathogenic	-1.174	Destabilizing	0.999	D	0.897	deleterious	N	0.487178407	None	None	N
V/E	0.8538	likely_pathogenic	0.8757	pathogenic	-1.012	Destabilizing	0.999	D	0.902	deleterious	None	None	None	None	N
V/F	0.3936	ambiguous	0.4126	ambiguous	-0.778	Destabilizing	0.999	D	0.837	deleterious	N	0.475061633	None	None	N
V/G	0.7098	likely_pathogenic	0.7583	pathogenic	-1.931	Destabilizing	0.999	D	0.899	deleterious	N	0.487178407	None	None	N
V/H	0.9333	likely_pathogenic	0.9524	pathogenic	-1.438	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/I	0.0824	likely_benign	0.0854	benign	-0.183	Destabilizing	0.994	D	0.592	neutral	N	0.491790846	None	None	N
V/K	0.8666	likely_pathogenic	0.8888	pathogenic	-1.137	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
V/L	0.3766	ambiguous	0.4209	ambiguous	-0.183	Destabilizing	0.994	D	0.626	neutral	N	0.517822654	None	None	N
V/M	0.2588	likely_benign	0.2836	benign	-0.314	Destabilizing	0.999	D	0.665	prob.neutral	None	None	None	None	N
V/N	0.8358	likely_pathogenic	0.8875	pathogenic	-1.324	Destabilizing	0.999	D	0.911	deleterious	None	None	None	None	N
V/P	0.9586	likely_pathogenic	0.9744	pathogenic	-0.575	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
V/Q	0.816	likely_pathogenic	0.8569	pathogenic	-1.202	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
V/R	0.8348	likely_pathogenic	0.8576	pathogenic	-0.975	Destabilizing	0.999	D	0.909	deleterious	None	None	None	None	N
V/S	0.7135	likely_pathogenic	0.7893	pathogenic	-2.011	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
V/T	0.4861	ambiguous	0.5752	pathogenic	-1.691	Destabilizing	0.998	D	0.562	neutral	None	None	None	None	N
V/W	0.9676	likely_pathogenic	0.9761	pathogenic	-1.112	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/Y	0.8651	likely_pathogenic	0.8893	pathogenic	-0.714	Destabilizing	0.999	D	0.82	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.