TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26476	79651;79652;79653	chr2:178566706;178566705;178566704	chr2:179431433;179431432;179431431
N2AB	24835	74728;74729;74730	chr2:178566706;178566705;178566704	chr2:179431433;179431432;179431431
N2A	23908	71947;71948;71949	chr2:178566706;178566705;178566704	chr2:179431433;179431432;179431431
N2B	17411	52456;52457;52458	chr2:178566706;178566705;178566704	chr2:179431433;179431432;179431431
Novex-1	17536	52831;52832;52833	chr2:178566706;178566705;178566704	chr2:179431433;179431432;179431431
Novex-2	17603	53032;53033;53034	chr2:178566706;178566705;178566704	chr2:179431433;179431432;179431431
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-80
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.1579
• 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
T/I	rs1457082371	None	0.93	N	0.621	0.326	0.351830644314	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85901E-06	0	0
T/P	None	None	0.006	N	0.422	0.219	0.238096912614	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1949	likely_benign	0.146	benign	-0.783	Destabilizing	0.278	N	0.483	neutral	N	0.472224023	None	None	N
T/C	0.605	likely_pathogenic	0.4857	ambiguous	-0.282	Destabilizing	0.995	D	0.619	neutral	None	None	None	None	N
T/D	0.9139	likely_pathogenic	0.8945	pathogenic	-0.629	Destabilizing	0.712	D	0.585	neutral	None	None	None	None	N
T/E	0.9444	likely_pathogenic	0.9334	pathogenic	-0.431	Destabilizing	0.712	D	0.591	neutral	None	None	None	None	N
T/F	0.9212	likely_pathogenic	0.8766	pathogenic	-0.496	Destabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	N
T/G	0.3508	ambiguous	0.2887	benign	-1.195	Destabilizing	0.553	D	0.627	neutral	None	None	None	None	N
T/H	0.887	likely_pathogenic	0.8535	pathogenic	-1.191	Destabilizing	0.995	D	0.73	deleterious	None	None	None	None	N
T/I	0.8818	likely_pathogenic	0.8347	pathogenic	0.295	Stabilizing	0.93	D	0.621	neutral	N	0.470956575	None	None	N
T/K	0.9556	likely_pathogenic	0.947	pathogenic	-0.007	Destabilizing	0.651	D	0.587	neutral	N	0.495697102	None	None	N
T/L	0.5695	likely_pathogenic	0.4845	ambiguous	0.295	Stabilizing	0.712	D	0.613	neutral	None	None	None	None	N
T/M	0.39	ambiguous	0.3226	benign	0.166	Stabilizing	0.995	D	0.615	neutral	None	None	None	None	N
T/N	0.5989	likely_pathogenic	0.5438	ambiguous	-0.655	Destabilizing	0.712	D	0.592	neutral	None	None	None	None	N
T/P	0.7722	likely_pathogenic	0.7573	pathogenic	-0.032	Destabilizing	0.006	N	0.422	neutral	N	0.485354755	None	None	N
T/Q	0.8935	likely_pathogenic	0.8698	pathogenic	-0.414	Destabilizing	0.946	D	0.608	neutral	None	None	None	None	N
T/R	0.9368	likely_pathogenic	0.9238	pathogenic	-0.255	Destabilizing	0.868	D	0.613	neutral	N	0.484340797	None	None	N
T/S	0.1115	likely_benign	0.0997	benign	-0.955	Destabilizing	0.01	N	0.321	neutral	N	0.370059288	None	None	N
T/V	0.6384	likely_pathogenic	0.5441	ambiguous	-0.032	Destabilizing	0.712	D	0.573	neutral	None	None	None	None	N
T/W	0.9786	likely_pathogenic	0.9736	pathogenic	-0.642	Destabilizing	0.995	D	0.77	deleterious	None	None	None	None	N
T/Y	0.9357	likely_pathogenic	0.9122	pathogenic	-0.213	Destabilizing	0.982	D	0.71	prob.delet.	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.