TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25635	77128;77129;77130	chr2:178569229;178569228;178569227	chr2:179433956;179433955;179433954
N2AB	23994	72205;72206;72207	chr2:178569229;178569228;178569227	chr2:179433956;179433955;179433954
N2A	23067	69424;69425;69426	chr2:178569229;178569228;178569227	chr2:179433956;179433955;179433954
N2B	16570	49933;49934;49935	chr2:178569229;178569228;178569227	chr2:179433956;179433955;179433954
Novex-1	16695	50308;50309;50310	chr2:178569229;178569228;178569227	chr2:179433956;179433955;179433954
Novex-2	16762	50509;50510;50511	chr2:178569229;178569228;178569227	chr2:179433956;179433955;179433954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-74
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1192
• 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
N/K	None	None	0.939	N	0.629	0.266	0.141422826196	gnomAD-4.0.0	6.88841E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03778E-07	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
N/A	0.7426	likely_pathogenic	0.7224	pathogenic	-0.76	Destabilizing	0.1	N	0.637	neutral	None	None	None	None	N
N/C	0.5343	ambiguous	0.5007	ambiguous	-0.199	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
N/D	0.7162	likely_pathogenic	0.7013	pathogenic	-1.695	Destabilizing	0.555	D	0.559	neutral	N	0.480914664	None	None	N
N/E	0.9431	likely_pathogenic	0.9372	pathogenic	-1.495	Destabilizing	0.846	D	0.59	neutral	None	None	None	None	N
N/F	0.8757	likely_pathogenic	0.8809	pathogenic	-0.282	Destabilizing	0.973	D	0.789	deleterious	None	None	None	None	N
N/G	0.5398	ambiguous	0.5182	ambiguous	-1.152	Destabilizing	0.851	D	0.562	neutral	None	None	None	None	N
N/H	0.2353	likely_benign	0.24	benign	-0.933	Destabilizing	0.018	N	0.188	neutral	N	0.462665591	None	None	N
N/I	0.9288	likely_pathogenic	0.9196	pathogenic	0.273	Stabilizing	0.953	D	0.785	deleterious	N	0.512705856	None	None	N
N/K	0.8909	likely_pathogenic	0.8862	pathogenic	-0.409	Destabilizing	0.939	D	0.629	neutral	N	0.468188779	None	None	N
N/L	0.8513	likely_pathogenic	0.8349	pathogenic	0.273	Stabilizing	0.794	D	0.735	prob.delet.	None	None	None	None	N
N/M	0.8548	likely_pathogenic	0.8454	pathogenic	0.58	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
N/P	0.9968	likely_pathogenic	0.9963	pathogenic	-0.042	Destabilizing	0.921	D	0.758	deleterious	None	None	None	None	N
N/Q	0.8087	likely_pathogenic	0.8028	pathogenic	-0.971	Destabilizing	0.982	D	0.682	prob.neutral	None	None	None	None	N
N/R	0.8593	likely_pathogenic	0.8552	pathogenic	-0.691	Destabilizing	0.954	D	0.662	neutral	None	None	None	None	N
N/S	0.233	likely_benign	0.2239	benign	-1.212	Destabilizing	0.047	N	0.225	neutral	N	0.47878705	None	None	N
N/T	0.6583	likely_pathogenic	0.6283	pathogenic	-0.837	Destabilizing	0.491	N	0.609	neutral	N	0.481977848	None	None	N
N/V	0.9055	likely_pathogenic	0.8911	pathogenic	-0.042	Destabilizing	0.392	N	0.763	deleterious	None	None	None	None	N
N/W	0.953	likely_pathogenic	0.9548	pathogenic	-0.289	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
N/Y	0.3564	ambiguous	0.3737	ambiguous	0.065	Stabilizing	0.046	N	0.609	neutral	N	0.482484827	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.