TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27437	82534;82535;82536	chr2:178563823;178563822;178563821	chr2:179428550;179428549;179428548
N2AB	25796	77611;77612;77613	chr2:178563823;178563822;178563821	chr2:179428550;179428549;179428548
N2A	24869	74830;74831;74832	chr2:178563823;178563822;178563821	chr2:179428550;179428549;179428548
N2B	18372	55339;55340;55341	chr2:178563823;178563822;178563821	chr2:179428550;179428549;179428548
Novex-1	18497	55714;55715;55716	chr2:178563823;178563822;178563821	chr2:179428550;179428549;179428548
Novex-2	18564	55915;55916;55917	chr2:178563823;178563822;178563821	chr2:179428550;179428549;179428548
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-87
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.4346
• 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	rs1431238411	-0.592	0.048	N	0.673	0.292	0.170165803431	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
G/S	rs1431238411	-0.592	0.048	N	0.673	0.292	0.170165803431	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85847E-06	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	0.456	ambiguous	0.4721	ambiguous	-0.513	Destabilizing	0.775	D	0.625	neutral	N	0.48658402	None	None	N
G/C	0.5094	ambiguous	0.5224	ambiguous	-0.826	Destabilizing	0.995	D	0.865	deleterious	D	0.54802681	None	None	N
G/D	0.3606	ambiguous	0.3905	ambiguous	-1.102	Destabilizing	0.924	D	0.805	deleterious	D	0.529896235	None	None	N
G/E	0.5032	ambiguous	0.5135	ambiguous	-1.27	Destabilizing	0.941	D	0.872	deleterious	None	None	None	None	N
G/F	0.8565	likely_pathogenic	0.8704	pathogenic	-1.282	Destabilizing	0.996	D	0.881	deleterious	None	None	None	None	N
G/H	0.5738	likely_pathogenic	0.607	pathogenic	-0.823	Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
G/I	0.8964	likely_pathogenic	0.9065	pathogenic	-0.601	Destabilizing	0.992	D	0.881	deleterious	None	None	None	None	N
G/K	0.6507	likely_pathogenic	0.6566	pathogenic	-1.036	Destabilizing	0.941	D	0.876	deleterious	None	None	None	None	N
G/L	0.7945	likely_pathogenic	0.8139	pathogenic	-0.601	Destabilizing	0.97	D	0.876	deleterious	None	None	None	None	N
G/M	0.8209	likely_pathogenic	0.8295	pathogenic	-0.372	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
G/N	0.3048	likely_benign	0.3513	ambiguous	-0.629	Destabilizing	0.941	D	0.826	deleterious	None	None	None	None	N
G/P	0.9903	likely_pathogenic	0.9921	pathogenic	-0.538	Destabilizing	0.97	D	0.893	deleterious	None	None	None	None	N
G/Q	0.5263	ambiguous	0.5356	ambiguous	-0.989	Destabilizing	0.992	D	0.893	deleterious	None	None	None	None	N
G/R	0.531	ambiguous	0.5383	ambiguous	-0.493	Destabilizing	0.96	D	0.896	deleterious	N	0.520261316	None	None	N
G/S	0.2017	likely_benign	0.2266	benign	-0.729	Destabilizing	0.048	N	0.673	neutral	N	0.489520082	None	None	N
G/T	0.5405	ambiguous	0.5676	pathogenic	-0.844	Destabilizing	0.941	D	0.865	deleterious	None	None	None	None	N
G/V	0.8043	likely_pathogenic	0.8128	pathogenic	-0.538	Destabilizing	0.96	D	0.885	deleterious	N	0.521021785	None	None	N
G/W	0.7747	likely_pathogenic	0.7834	pathogenic	-1.434	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
G/Y	0.7158	likely_pathogenic	0.7482	pathogenic	-1.099	Destabilizing	0.996	D	0.875	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.