TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26033	78322;78323;78324	chr2:178568035;178568034;178568033	chr2:179432762;179432761;179432760
N2AB	24392	73399;73400;73401	chr2:178568035;178568034;178568033	chr2:179432762;179432761;179432760
N2A	23465	70618;70619;70620	chr2:178568035;178568034;178568033	chr2:179432762;179432761;179432760
N2B	16968	51127;51128;51129	chr2:178568035;178568034;178568033	chr2:179432762;179432761;179432760
Novex-1	17093	51502;51503;51504	chr2:178568035;178568034;178568033	chr2:179432762;179432761;179432760
Novex-2	17160	51703;51704;51705	chr2:178568035;178568034;178568033	chr2:179432762;179432761;179432760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-77
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.864
• Predicted PPI site: I

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/D	rs1343439092	0.412	0.958	N	0.481	0.333	0.180583059064	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	6.50195E-04	None	0	None	0	0	0
N/D	rs1343439092	0.412	0.958	N	0.481	0.333	0.180583059064	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.93424E-04	None	0	0	0	0	0
N/D	rs1343439092	0.412	0.958	N	0.481	0.333	0.180583059064	gnomAD-4.0.0	6.57471E-06	None	None	None	None	I	None	0	0	None	0	1.93424E-04	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
N/A	0.7414	likely_pathogenic	0.7659	pathogenic	-0.12	Destabilizing	0.968	D	0.434	neutral	None	None	None	None	I
N/C	0.7252	likely_pathogenic	0.7228	pathogenic	0.127	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
N/D	0.6689	likely_pathogenic	0.6901	pathogenic	0.011	Stabilizing	0.958	D	0.481	neutral	N	0.49121763	None	None	I
N/E	0.933	likely_pathogenic	0.9467	pathogenic	-0.056	Destabilizing	0.968	D	0.462	neutral	None	None	None	None	I
N/F	0.9169	likely_pathogenic	0.9265	pathogenic	-0.729	Destabilizing	0.995	D	0.611	neutral	None	None	None	None	I
N/G	0.5949	likely_pathogenic	0.6315	pathogenic	-0.203	Destabilizing	0.968	D	0.44	neutral	None	None	None	None	I
N/H	0.4078	ambiguous	0.4271	ambiguous	-0.216	Destabilizing	0.142	N	0.337	neutral	N	0.483413561	None	None	I
N/I	0.8172	likely_pathogenic	0.8336	pathogenic	0.001	Stabilizing	0.994	D	0.613	neutral	N	0.495023356	None	None	I
N/K	0.8861	likely_pathogenic	0.91	pathogenic	0.11	Stabilizing	0.958	D	0.458	neutral	N	0.513057126	None	None	I
N/L	0.7036	likely_pathogenic	0.7358	pathogenic	0.001	Stabilizing	0.991	D	0.593	neutral	None	None	None	None	I
N/M	0.7823	likely_pathogenic	0.81	pathogenic	0.106	Stabilizing	1.0	D	0.55	neutral	None	None	None	None	I
N/P	0.9352	likely_pathogenic	0.9443	pathogenic	-0.017	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	I
N/Q	0.8526	likely_pathogenic	0.8737	pathogenic	-0.319	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	I
N/R	0.8915	likely_pathogenic	0.9072	pathogenic	0.193	Stabilizing	0.991	D	0.507	neutral	None	None	None	None	I
N/S	0.1941	likely_benign	0.2138	benign	-0.066	Destabilizing	0.958	D	0.444	neutral	N	0.468092841	None	None	I
N/T	0.4567	ambiguous	0.477	ambiguous	-0.022	Destabilizing	0.979	D	0.46	neutral	N	0.506592514	None	None	I
N/V	0.8062	likely_pathogenic	0.8261	pathogenic	-0.017	Destabilizing	0.995	D	0.595	neutral	None	None	None	None	I
N/W	0.9731	likely_pathogenic	0.9759	pathogenic	-0.857	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
N/Y	0.5518	ambiguous	0.5859	pathogenic	-0.533	Destabilizing	0.976	D	0.531	neutral	N	0.495023356	None	None	I

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.