TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25863	77812;77813;77814	chr2:178568545;178568544;178568543	chr2:179433272;179433271;179433270
N2AB	24222	72889;72890;72891	chr2:178568545;178568544;178568543	chr2:179433272;179433271;179433270
N2A	23295	70108;70109;70110	chr2:178568545;178568544;178568543	chr2:179433272;179433271;179433270
N2B	16798	50617;50618;50619	chr2:178568545;178568544;178568543	chr2:179433272;179433271;179433270
Novex-1	16923	50992;50993;50994	chr2:178568545;178568544;178568543	chr2:179433272;179433271;179433270
Novex-2	16990	51193;51194;51195	chr2:178568545;178568544;178568543	chr2:179433272;179433271;179433270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-136
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.8584
• 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/G	rs1171070025	0.054	0.645	N	0.485	0.227	0.18995819373	gnomAD-4.0.0	1.59193E-06	None	None	None	None	N	None	0	2.28686E-05	None	0	0	None	0	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
D/A	0.1053	likely_benign	0.1062	benign	-0.143	Destabilizing	0.477	N	0.459	neutral	N	0.465366675	None	None	N
D/C	0.5115	ambiguous	0.4851	ambiguous	0.114	Stabilizing	0.995	D	0.635	neutral	None	None	None	None	N
D/E	0.0883	likely_benign	0.0816	benign	-0.113	Destabilizing	0.002	N	0.272	neutral	N	0.368952062	None	None	N
D/F	0.4879	ambiguous	0.4823	ambiguous	-0.29	Destabilizing	0.981	D	0.594	neutral	None	None	None	None	N
D/G	0.1182	likely_benign	0.1144	benign	-0.294	Destabilizing	0.645	D	0.485	neutral	N	0.476218387	None	None	N
D/H	0.2596	likely_benign	0.2543	benign	-0.029	Destabilizing	0.98	D	0.452	neutral	N	0.497729809	None	None	N
D/I	0.2386	likely_benign	0.229	benign	0.195	Stabilizing	0.945	D	0.606	neutral	None	None	None	None	N
D/K	0.2685	likely_benign	0.2652	benign	0.268	Stabilizing	0.547	D	0.477	neutral	None	None	None	None	N
D/L	0.2666	likely_benign	0.271	benign	0.195	Stabilizing	0.894	D	0.597	neutral	None	None	None	None	N
D/M	0.4095	ambiguous	0.392	ambiguous	0.271	Stabilizing	0.995	D	0.591	neutral	None	None	None	None	N
D/N	0.089	likely_benign	0.0863	benign	0.272	Stabilizing	0.645	D	0.449	neutral	N	0.478565259	None	None	N
D/P	0.6272	likely_pathogenic	0.6456	pathogenic	0.103	Stabilizing	0.945	D	0.475	neutral	None	None	None	None	N
D/Q	0.2216	likely_benign	0.216	benign	0.265	Stabilizing	0.809	D	0.431	neutral	None	None	None	None	N
D/R	0.3454	ambiguous	0.3401	ambiguous	0.428	Stabilizing	0.894	D	0.539	neutral	None	None	None	None	N
D/S	0.0943	likely_benign	0.0909	benign	0.088	Stabilizing	0.547	D	0.447	neutral	None	None	None	None	N
D/T	0.1499	likely_benign	0.1464	benign	0.193	Stabilizing	0.894	D	0.441	neutral	None	None	None	None	N
D/V	0.1375	likely_benign	0.1361	benign	0.103	Stabilizing	0.864	D	0.59	neutral	N	0.497903168	None	None	N
D/W	0.8129	likely_pathogenic	0.8103	pathogenic	-0.25	Destabilizing	0.995	D	0.649	neutral	None	None	None	None	N
D/Y	0.1973	likely_benign	0.2066	benign	-0.077	Destabilizing	0.975	D	0.595	neutral	N	0.514603417	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.