TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1920	5983;5984;5985	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831
N2AB	1920	5983;5984;5985	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831
N2A	1920	5983;5984;5985	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831
N2B	1874	5845;5846;5847	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831
Novex-1	1874	5845;5846;5847	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831
Novex-2	1874	5845;5846;5847	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831
Novex-3	1920	5983;5984;5985	chr2:178776106;178776105;178776104	chr2:179640833;179640832;179640831

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-9
• Domain position: 80
• Structural Position: 165
• Q(SASA): 0.4209
• 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
V/M	rs773719613	-0.327	0.863	N	0.4	0.198	0.596401026678	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.81E-06	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	0.1485	likely_benign	0.1691	benign	-0.757	Destabilizing	0.244	N	0.231	neutral	N	0.460835126	None	None	I
V/C	0.6087	likely_pathogenic	0.5857	pathogenic	-0.663	Destabilizing	0.981	D	0.48	neutral	None	None	None	None	I
V/D	0.3779	ambiguous	0.4666	ambiguous	-0.66	Destabilizing	0.828	D	0.595	neutral	None	None	None	None	I
V/E	0.2658	likely_benign	0.3086	benign	-0.767	Destabilizing	0.642	D	0.575	neutral	N	0.399604071	None	None	I
V/F	0.1465	likely_benign	0.1686	benign	-0.87	Destabilizing	0.007	N	0.289	neutral	None	None	None	None	I
V/G	0.2104	likely_benign	0.247	benign	-0.92	Destabilizing	0.784	D	0.598	neutral	N	0.494831948	None	None	I
V/H	0.4656	ambiguous	0.5125	ambiguous	-0.445	Destabilizing	0.981	D	0.549	neutral	None	None	None	None	I
V/I	0.0706	likely_benign	0.0697	benign	-0.467	Destabilizing	0.003	N	0.177	neutral	None	None	None	None	I
V/K	0.2882	likely_benign	0.3361	benign	-0.704	Destabilizing	0.031	N	0.349	neutral	None	None	None	None	I
V/L	0.179	likely_benign	0.2002	benign	-0.467	Destabilizing	0.139	N	0.21	neutral	N	0.494968389	None	None	I
V/M	0.1029	likely_benign	0.1117	benign	-0.419	Destabilizing	0.863	D	0.4	neutral	N	0.485752372	None	None	I
V/N	0.1738	likely_benign	0.1933	benign	-0.407	Destabilizing	0.828	D	0.561	neutral	None	None	None	None	I
V/P	0.8722	likely_pathogenic	0.9117	pathogenic	-0.528	Destabilizing	0.981	D	0.557	neutral	None	None	None	None	I
V/Q	0.2436	likely_benign	0.2652	benign	-0.688	Destabilizing	0.893	D	0.553	neutral	None	None	None	None	I
V/R	0.2974	likely_benign	0.3622	ambiguous	-0.097	Destabilizing	0.543	D	0.567	neutral	None	None	None	None	I
V/S	0.1512	likely_benign	0.1608	benign	-0.761	Destabilizing	0.329	N	0.561	neutral	None	None	None	None	I
V/T	0.1141	likely_benign	0.1207	benign	-0.772	Destabilizing	0.013	N	0.146	neutral	None	None	None	None	I
V/W	0.7933	likely_pathogenic	0.8383	pathogenic	-0.939	Destabilizing	0.995	D	0.551	neutral	None	None	None	None	I
V/Y	0.4997	ambiguous	0.5289	ambiguous	-0.666	Destabilizing	0.543	D	0.488	neutral	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.