TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7712	23359;23360;23361	chr2:178720628;178720627;178720626	chr2:179585355;179585354;179585353
N2AB	7395	22408;22409;22410	chr2:178720628;178720627;178720626	chr2:179585355;179585354;179585353
N2A	6468	19627;19628;19629	chr2:178720628;178720627;178720626	chr2:179585355;179585354;179585353
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-62
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.4578
• 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
G/R	None	None	0.801	N	0.434	0.252	0.540518506614	gnomAD-4.0.0	2.06262E-06	None	None	None	None	I	None	0	0	None	0	2.52551E-05	None	0	0	0	1.18304E-05	1.66617E-05

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	0.0832	likely_benign	0.0864	benign	-0.367	Destabilizing	0.625	D	0.355	neutral	N	0.376308548	None	None	I
G/C	0.2063	likely_benign	0.2176	benign	-0.861	Destabilizing	0.998	D	0.468	neutral	None	None	None	None	I
G/D	0.1813	likely_benign	0.2196	benign	-0.726	Destabilizing	0.007	N	0.114	neutral	None	None	None	None	I
G/E	0.1403	likely_benign	0.1617	benign	-0.842	Destabilizing	0.005	N	0.166	neutral	N	0.319895118	None	None	I
G/F	0.452	ambiguous	0.4685	ambiguous	-0.864	Destabilizing	0.991	D	0.457	neutral	None	None	None	None	I
G/H	0.3755	ambiguous	0.4141	ambiguous	-0.789	Destabilizing	0.974	D	0.433	neutral	None	None	None	None	I
G/I	0.177	likely_benign	0.1932	benign	-0.273	Destabilizing	0.974	D	0.477	neutral	None	None	None	None	I
G/K	0.4532	ambiguous	0.5059	ambiguous	-1.113	Destabilizing	0.728	D	0.402	neutral	None	None	None	None	I
G/L	0.2555	likely_benign	0.2835	benign	-0.273	Destabilizing	0.842	D	0.454	neutral	None	None	None	None	I
G/M	0.3217	likely_benign	0.3473	ambiguous	-0.381	Destabilizing	0.998	D	0.439	neutral	None	None	None	None	I
G/N	0.2457	likely_benign	0.2714	benign	-0.75	Destabilizing	0.728	D	0.288	neutral	None	None	None	None	I
G/P	0.5854	likely_pathogenic	0.609	pathogenic	-0.266	Destabilizing	0.974	D	0.46	neutral	None	None	None	None	I
G/Q	0.2932	likely_benign	0.3294	benign	-0.965	Destabilizing	0.172	N	0.273	neutral	None	None	None	None	I
G/R	0.3439	ambiguous	0.3909	ambiguous	-0.712	Destabilizing	0.801	D	0.434	neutral	N	0.388488412	None	None	I
G/S	0.0854	likely_benign	0.0907	benign	-0.921	Destabilizing	0.688	D	0.325	neutral	None	None	None	None	I
G/T	0.1139	likely_benign	0.1211	benign	-0.959	Destabilizing	0.842	D	0.418	neutral	None	None	None	None	I
G/V	0.1147	likely_benign	0.1253	benign	-0.266	Destabilizing	0.891	D	0.455	neutral	N	0.373478887	None	None	I
G/W	0.3431	ambiguous	0.3667	ambiguous	-1.132	Destabilizing	0.998	D	0.481	neutral	None	None	None	None	I
G/Y	0.3545	ambiguous	0.3787	ambiguous	-0.75	Destabilizing	0.991	D	0.471	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.