TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7361	22306;22307;22308	chr2:178722818;178722817;178722816	chr2:179587545;179587544;179587543
N2AB	7044	21355;21356;21357	chr2:178722818;178722817;178722816	chr2:179587545;179587544;179587543
N2A	6117	18574;18575;18576	chr2:178722818;178722817;178722816	chr2:179587545;179587544;179587543
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-58
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.5647
• 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
T/A	None	None	0.046	N	0.211	0.111	0.168933306366	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	0	0
T/N	rs1425492375	0.018	0.623	N	0.267	0.204	0.350524144436	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
T/N	rs1425492375	0.018	0.623	N	0.267	0.204	0.350524144436	gnomAD-4.0.0	4.7767E-06	None	None	None	None	N	None	0	0	None	0	2.77454E-05	None	0	0	2.85972E-06	1.43328E-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
T/A	0.0929	likely_benign	0.133	benign	-0.52	Destabilizing	0.046	N	0.211	neutral	N	0.474683244	None	None	N
T/C	0.5642	likely_pathogenic	0.7084	pathogenic	-0.409	Destabilizing	0.998	D	0.343	neutral	None	None	None	None	N
T/D	0.4395	ambiguous	0.6481	pathogenic	0.49	Stabilizing	0.686	D	0.327	neutral	None	None	None	None	N
T/E	0.3049	likely_benign	0.4815	ambiguous	0.463	Stabilizing	0.879	D	0.337	neutral	None	None	None	None	N
T/F	0.2712	likely_benign	0.4375	ambiguous	-0.868	Destabilizing	0.079	N	0.267	neutral	None	None	None	None	N
T/G	0.2667	likely_benign	0.3963	ambiguous	-0.702	Destabilizing	0.024	N	0.24	neutral	None	None	None	None	N
T/H	0.2745	likely_benign	0.42	ambiguous	-0.852	Destabilizing	0.995	D	0.361	neutral	None	None	None	None	N
T/I	0.1743	likely_benign	0.2901	benign	-0.149	Destabilizing	0.794	D	0.329	neutral	N	0.460812657	None	None	N
T/K	0.1965	likely_benign	0.321	benign	-0.313	Destabilizing	0.12	N	0.211	neutral	None	None	None	None	N
T/L	0.1165	likely_benign	0.1844	benign	-0.149	Destabilizing	0.678	D	0.321	neutral	None	None	None	None	N
T/M	0.095	likely_benign	0.1276	benign	-0.181	Destabilizing	0.986	D	0.343	neutral	None	None	None	None	N
T/N	0.1437	likely_benign	0.2284	benign	-0.263	Destabilizing	0.623	D	0.267	neutral	N	0.478878343	None	None	N
T/P	0.4655	ambiguous	0.6432	pathogenic	-0.242	Destabilizing	0.922	D	0.359	neutral	D	0.522130474	None	None	N
T/Q	0.2066	likely_benign	0.3116	benign	-0.366	Destabilizing	0.944	D	0.361	neutral	None	None	None	None	N
T/R	0.1506	likely_benign	0.2354	benign	-0.102	Destabilizing	0.932	D	0.372	neutral	None	None	None	None	N
T/S	0.1191	likely_benign	0.1783	benign	-0.547	Destabilizing	0.02	N	0.205	neutral	N	0.446301777	None	None	N
T/V	0.1396	likely_benign	0.2138	benign	-0.242	Destabilizing	0.089	N	0.182	neutral	None	None	None	None	N
T/W	0.6032	likely_pathogenic	0.7607	pathogenic	-0.873	Destabilizing	1.0	D	0.371	neutral	None	None	None	None	N
T/Y	0.3169	likely_benign	0.4867	ambiguous	-0.583	Destabilizing	0.98	D	0.391	neutral	None	None	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.