TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26894	80905;80906;80907	chr2:178565452;178565451;178565450	chr2:179430179;179430178;179430177
N2AB	25253	75982;75983;75984	chr2:178565452;178565451;178565450	chr2:179430179;179430178;179430177
N2A	24326	73201;73202;73203	chr2:178565452;178565451;178565450	chr2:179430179;179430178;179430177
N2B	17829	53710;53711;53712	chr2:178565452;178565451;178565450	chr2:179430179;179430178;179430177
Novex-1	17954	54085;54086;54087	chr2:178565452;178565451;178565450	chr2:179430179;179430178;179430177
Novex-2	18021	54286;54287;54288	chr2:178565452;178565451;178565450	chr2:179430179;179430178;179430177
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-139
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.282
• 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/A	rs928657933	None	0.928	D	0.621	0.836	0.634485840324	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/A	rs928657933	None	0.928	D	0.621	0.836	0.634485840324	gnomAD-4.0.0	1.85971E-06	None	None	None	None	I	None	2.67194E-05	0	None	0	0	None	0	0	0	0	1.6021E-05
G/E	None	None	0.978	D	0.79	0.774	0.77413480687	gnomAD-4.0.0	6.84418E-07	None	None	None	None	I	None	0	0	None	0	0	None	1.87378E-05	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
G/A	0.3441	ambiguous	0.3268	benign	-0.467	Destabilizing	0.928	D	0.621	neutral	D	0.624522461	None	None	I
G/C	0.4398	ambiguous	0.441	ambiguous	-0.871	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	I
G/D	0.4241	ambiguous	0.4209	ambiguous	-1.032	Destabilizing	0.992	D	0.805	deleterious	None	None	None	None	I
G/E	0.4323	ambiguous	0.4277	ambiguous	-1.203	Destabilizing	0.978	D	0.79	deleterious	D	0.605233153	None	None	I
G/F	0.8383	likely_pathogenic	0.8335	pathogenic	-1.215	Destabilizing	0.983	D	0.809	deleterious	None	None	None	None	I
G/H	0.5078	ambiguous	0.5073	ambiguous	-0.727	Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	I
G/I	0.8065	likely_pathogenic	0.7978	pathogenic	-0.587	Destabilizing	0.968	D	0.789	deleterious	None	None	None	None	I
G/K	0.4524	ambiguous	0.4421	ambiguous	-1.016	Destabilizing	0.968	D	0.774	deleterious	None	None	None	None	I
G/L	0.7328	likely_pathogenic	0.7231	pathogenic	-0.587	Destabilizing	0.11	N	0.597	neutral	None	None	None	None	I
G/M	0.735	likely_pathogenic	0.7245	pathogenic	-0.437	Destabilizing	0.996	D	0.821	deleterious	None	None	None	None	I
G/N	0.3659	ambiguous	0.375	ambiguous	-0.621	Destabilizing	0.983	D	0.796	deleterious	None	None	None	None	I
G/P	0.9657	likely_pathogenic	0.9674	pathogenic	-0.514	Destabilizing	0.997	D	0.814	deleterious	None	None	None	None	I
G/Q	0.4117	ambiguous	0.4103	ambiguous	-0.979	Destabilizing	0.983	D	0.815	deleterious	None	None	None	None	I
G/R	0.3486	ambiguous	0.3344	benign	-0.468	Destabilizing	0.175	N	0.581	neutral	D	0.640975791	None	None	I
G/S	0.1835	likely_benign	0.1792	benign	-0.719	Destabilizing	0.983	D	0.783	deleterious	None	None	None	None	I
G/T	0.4146	ambiguous	0.3994	ambiguous	-0.836	Destabilizing	0.983	D	0.79	deleterious	None	None	None	None	I
G/V	0.6839	likely_pathogenic	0.6601	pathogenic	-0.514	Destabilizing	0.957	D	0.785	deleterious	D	0.666715707	None	None	I
G/W	0.6576	likely_pathogenic	0.6639	pathogenic	-1.35	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
G/Y	0.7258	likely_pathogenic	0.7211	pathogenic	-1.023	Destabilizing	0.999	D	0.824	deleterious	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.