TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2685	8278;8279;8280	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999
N2AB	2685	8278;8279;8280	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999
N2A	2685	8278;8279;8280	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999
N2B	2639	8140;8141;8142	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999
Novex-1	2639	8140;8141;8142	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999
Novex-2	2639	8140;8141;8142	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999
Novex-3	2685	8278;8279;8280	chr2:178771274;178771273;178771272	chr2:179636001;179636000;179635999

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-16
• Domain position: 65
• Structural Position: 149
• Q(SASA): 0.1984
• 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
D/H	None	None	1.0	D	0.795	0.613	0.738525484636	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/H	None	None	1.0	D	0.795	0.613	0.738525484636	gnomAD-4.0.0	6.57194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46964E-05	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
D/A	0.6591	likely_pathogenic	0.6816	pathogenic	0.134	Stabilizing	1.0	D	0.808	deleterious	D	0.793150483	None	None	N
D/C	0.8915	likely_pathogenic	0.908	pathogenic	0.138	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/E	0.5787	likely_pathogenic	0.6184	pathogenic	-0.619	Destabilizing	1.0	D	0.595	neutral	D	0.794314007	None	None	N
D/F	0.918	likely_pathogenic	0.9277	pathogenic	0.868	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
D/G	0.7294	likely_pathogenic	0.7357	pathogenic	-0.328	Destabilizing	1.0	D	0.777	deleterious	D	0.792380202	None	None	N
D/H	0.6164	likely_pathogenic	0.6282	pathogenic	0.482	Stabilizing	1.0	D	0.795	deleterious	D	0.709520678	None	None	N
D/I	0.8956	likely_pathogenic	0.9094	pathogenic	1.378	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/K	0.9182	likely_pathogenic	0.9112	pathogenic	-0.056	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
D/L	0.8906	likely_pathogenic	0.9066	pathogenic	1.378	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/M	0.9197	likely_pathogenic	0.9329	pathogenic	1.774	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/N	0.2496	likely_benign	0.2794	benign	-0.803	Destabilizing	1.0	D	0.78	deleterious	D	0.794770238	None	None	N
D/P	0.995	likely_pathogenic	0.9937	pathogenic	0.993	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
D/Q	0.7935	likely_pathogenic	0.8018	pathogenic	-0.496	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
D/R	0.933	likely_pathogenic	0.9264	pathogenic	0.038	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/S	0.4226	ambiguous	0.4519	ambiguous	-1.099	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/T	0.7718	likely_pathogenic	0.7912	pathogenic	-0.687	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
D/V	0.7652	likely_pathogenic	0.7911	pathogenic	0.993	Stabilizing	1.0	D	0.804	deleterious	D	0.7923515	None	None	N
D/W	0.9841	likely_pathogenic	0.9853	pathogenic	0.958	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
D/Y	0.6033	likely_pathogenic	0.6219	pathogenic	1.131	Stabilizing	1.0	D	0.828	deleterious	D	0.792447509	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.