TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14200	42823;42824;42825	chr2:178633901;178633900;178633899	chr2:179498628;179498627;179498626
N2AB	12559	37900;37901;37902	chr2:178633901;178633900;178633899	chr2:179498628;179498627;179498626
N2A	11632	35119;35120;35121	chr2:178633901;178633900;178633899	chr2:179498628;179498627;179498626
N2B	5135	15628;15629;15630	chr2:178633901;178633900;178633899	chr2:179498628;179498627;179498626
Novex-1	5260	16003;16004;16005	chr2:178633901;178633900;178633899	chr2:179498628;179498627;179498626
Novex-2	5327	16204;16205;16206	chr2:178633901;178633900;178633899	chr2:179498628;179498627;179498626
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-92
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.1562
• 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
M/R	None	None	0.106	N	0.719	0.529	0.635165634531	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
M/A	0.9409	likely_pathogenic	0.949	pathogenic	-2.639	Highly Destabilizing	0.014	N	0.544	neutral	None	None	None	None	N
M/C	0.9256	likely_pathogenic	0.9406	pathogenic	-2.629	Highly Destabilizing	0.628	D	0.721	prob.delet.	None	None	None	None	N
M/D	0.995	likely_pathogenic	0.9967	pathogenic	-1.838	Destabilizing	0.356	N	0.789	deleterious	None	None	None	None	N
M/E	0.9552	likely_pathogenic	0.9671	pathogenic	-1.65	Destabilizing	0.136	N	0.723	prob.delet.	None	None	None	None	N
M/F	0.367	ambiguous	0.3702	ambiguous	-1.111	Destabilizing	0.072	N	0.568	neutral	None	None	None	None	N
M/G	0.9799	likely_pathogenic	0.9869	pathogenic	-3.121	Highly Destabilizing	0.136	N	0.737	prob.delet.	None	None	None	None	N
M/H	0.9464	likely_pathogenic	0.9586	pathogenic	-2.401	Highly Destabilizing	0.628	D	0.775	deleterious	None	None	None	None	N
M/I	0.2829	likely_benign	0.2649	benign	-1.269	Destabilizing	None	N	0.298	neutral	N	0.286285887	None	None	N
M/K	0.8151	likely_pathogenic	0.8461	pathogenic	-1.564	Destabilizing	0.106	N	0.632	neutral	N	0.512000938	None	None	N
M/L	0.1796	likely_benign	0.1751	benign	-1.269	Destabilizing	None	N	0.283	neutral	N	0.425906051	None	None	N
M/N	0.9639	likely_pathogenic	0.9708	pathogenic	-1.789	Destabilizing	0.628	D	0.771	deleterious	None	None	None	None	N
M/P	0.9975	likely_pathogenic	0.9982	pathogenic	-1.705	Destabilizing	0.628	D	0.773	deleterious	None	None	None	None	N
M/Q	0.835	likely_pathogenic	0.8632	pathogenic	-1.585	Destabilizing	0.628	D	0.656	neutral	None	None	None	None	N
M/R	0.8246	likely_pathogenic	0.8532	pathogenic	-1.429	Destabilizing	0.106	N	0.719	prob.delet.	N	0.512000938	None	None	N
M/S	0.9625	likely_pathogenic	0.9689	pathogenic	-2.494	Highly Destabilizing	0.136	N	0.623	neutral	None	None	None	None	N
M/T	0.8846	likely_pathogenic	0.9056	pathogenic	-2.166	Highly Destabilizing	0.024	N	0.615	neutral	N	0.511490213	None	None	N
M/V	0.1993	likely_benign	0.2026	benign	-1.705	Destabilizing	0.001	N	0.345	neutral	N	0.435452602	None	None	N
M/W	0.7712	likely_pathogenic	0.8133	pathogenic	-1.247	Destabilizing	0.864	D	0.715	prob.delet.	None	None	None	None	N
M/Y	0.7587	likely_pathogenic	0.8013	pathogenic	-1.313	Destabilizing	0.356	N	0.721	prob.delet.	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.