TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20994	63205;63206;63207	chr2:178588745;178588744;178588743	chr2:179453472;179453471;179453470
N2AB	19353	58282;58283;58284	chr2:178588745;178588744;178588743	chr2:179453472;179453471;179453470
N2A	18426	55501;55502;55503	chr2:178588745;178588744;178588743	chr2:179453472;179453471;179453470
N2B	11929	36010;36011;36012	chr2:178588745;178588744;178588743	chr2:179453472;179453471;179453470
Novex-1	12054	36385;36386;36387	chr2:178588745;178588744;178588743	chr2:179453472;179453471;179453470
Novex-2	12121	36586;36587;36588	chr2:178588745;178588744;178588743	chr2:179453472;179453471;179453470
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-40
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6271
• 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
S/T	None	None	0.543	N	0.261	0.111	0.134241683229	gnomAD-4.0.0	1.59224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-05	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
S/A	0.0817	likely_benign	0.0784	benign	-0.339	Destabilizing	0.973	D	0.421	neutral	N	0.428302302	None	None	N
S/C	0.1201	likely_benign	0.1217	benign	-0.228	Destabilizing	1.0	D	0.597	neutral	N	0.518385588	None	None	N
S/D	0.3833	ambiguous	0.3472	ambiguous	0.006	Stabilizing	0.996	D	0.559	neutral	None	None	None	None	N
S/E	0.4341	ambiguous	0.4038	ambiguous	-0.09	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	N
S/F	0.3094	likely_benign	0.2981	benign	-0.915	Destabilizing	0.999	D	0.671	neutral	N	0.507168517	None	None	N
S/G	0.104	likely_benign	0.098	benign	-0.454	Destabilizing	0.996	D	0.452	neutral	None	None	None	None	N
S/H	0.3531	ambiguous	0.3397	benign	-0.97	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
S/I	0.1814	likely_benign	0.1812	benign	-0.167	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
S/K	0.5883	likely_pathogenic	0.5754	pathogenic	-0.534	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	N
S/L	0.123	likely_benign	0.117	benign	-0.167	Destabilizing	0.992	D	0.561	neutral	None	None	None	None	N
S/M	0.1744	likely_benign	0.174	benign	0.107	Stabilizing	1.0	D	0.596	neutral	None	None	None	None	N
S/N	0.1291	likely_benign	0.121	benign	-0.222	Destabilizing	0.996	D	0.546	neutral	None	None	None	None	N
S/P	0.0992	likely_benign	0.0853	benign	-0.196	Destabilizing	0.999	D	0.661	neutral	N	0.325769793	None	None	N
S/Q	0.4119	ambiguous	0.396	ambiguous	-0.493	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
S/R	0.5799	likely_pathogenic	0.5716	pathogenic	-0.3	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/T	0.0906	likely_benign	0.0882	benign	-0.319	Destabilizing	0.543	D	0.261	neutral	N	0.468167412	None	None	N
S/V	0.1833	likely_benign	0.1809	benign	-0.196	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	N
S/W	0.3938	ambiguous	0.3944	ambiguous	-0.929	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/Y	0.2288	likely_benign	0.2188	benign	-0.652	Destabilizing	0.999	D	0.661	neutral	N	0.518038872	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.