TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24831	74716;74717;74718	chr2:178571641;178571640;178571639	chr2:179436368;179436367;179436366
N2AB	23190	69793;69794;69795	chr2:178571641;178571640;178571639	chr2:179436368;179436367;179436366
N2A	22263	67012;67013;67014	chr2:178571641;178571640;178571639	chr2:179436368;179436367;179436366
N2B	15766	47521;47522;47523	chr2:178571641;178571640;178571639	chr2:179436368;179436367;179436366
Novex-1	15891	47896;47897;47898	chr2:178571641;178571640;178571639	chr2:179436368;179436367;179436366
Novex-2	15958	48097;48098;48099	chr2:178571641;178571640;178571639	chr2:179436368;179436367;179436366
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-68
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.21
• 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
G/S	rs1708234650	None	None	N	0.213	0.057	0.0482279557977	gnomAD-4.0.0	7.96128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	7.16476E-05	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
G/A	0.0869	likely_benign	0.0818	benign	-0.374	Destabilizing	0.012	N	0.346	neutral	N	0.409023108	None	None	N
G/C	0.1442	likely_benign	0.1306	benign	-0.679	Destabilizing	0.612	D	0.545	neutral	N	0.43295876	None	None	N
G/D	0.1157	likely_benign	0.0955	benign	-0.914	Destabilizing	None	N	0.325	neutral	N	0.345222345	None	None	N
G/E	0.0873	likely_benign	0.0864	benign	-0.83	Destabilizing	None	N	0.407	neutral	None	None	None	None	N
G/F	0.3698	ambiguous	0.3214	benign	-0.529	Destabilizing	0.356	N	0.538	neutral	None	None	None	None	N
G/H	0.238	likely_benign	0.2137	benign	-1.415	Destabilizing	0.214	N	0.515	neutral	None	None	None	None	N
G/I	0.1933	likely_benign	0.1682	benign	0.479	Stabilizing	0.214	N	0.559	neutral	None	None	None	None	N
G/K	0.2072	likely_benign	0.2069	benign	-0.82	Destabilizing	0.016	N	0.413	neutral	None	None	None	None	N
G/L	0.1713	likely_benign	0.1552	benign	0.479	Stabilizing	0.072	N	0.498	neutral	None	None	None	None	N
G/M	0.2255	likely_benign	0.207	benign	0.239	Stabilizing	0.356	N	0.537	neutral	None	None	None	None	N
G/N	0.1425	likely_benign	0.1222	benign	-0.779	Destabilizing	None	N	0.185	neutral	None	None	None	None	N
G/P	0.8282	likely_pathogenic	0.7857	pathogenic	0.242	Stabilizing	0.072	N	0.52	neutral	None	None	None	None	N
G/Q	0.1426	likely_benign	0.1386	benign	-0.69	Destabilizing	None	N	0.427	neutral	None	None	None	None	N
G/R	0.2123	likely_benign	0.2062	benign	-0.922	Destabilizing	0.029	N	0.467	neutral	N	0.401307701	None	None	N
G/S	0.0935	likely_benign	0.0844	benign	-1.157	Destabilizing	None	N	0.213	neutral	N	0.359284934	None	None	N
G/T	0.1331	likely_benign	0.1219	benign	-0.944	Destabilizing	0.016	N	0.426	neutral	None	None	None	None	N
G/V	0.1452	likely_benign	0.1292	benign	0.242	Stabilizing	0.055	N	0.512	neutral	N	0.420586895	None	None	N
G/W	0.3251	likely_benign	0.3011	benign	-1.183	Destabilizing	0.864	D	0.545	neutral	None	None	None	None	N
G/Y	0.2395	likely_benign	0.2087	benign	-0.556	Destabilizing	0.356	N	0.54	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.