TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25125	75598;75599;75600	chr2:178570759;178570758;178570757	chr2:179435486;179435485;179435484
N2AB	23484	70675;70676;70677	chr2:178570759;178570758;178570757	chr2:179435486;179435485;179435484
N2A	22557	67894;67895;67896	chr2:178570759;178570758;178570757	chr2:179435486;179435485;179435484
N2B	16060	48403;48404;48405	chr2:178570759;178570758;178570757	chr2:179435486;179435485;179435484
Novex-1	16185	48778;48779;48780	chr2:178570759;178570758;178570757	chr2:179435486;179435485;179435484
Novex-2	16252	48979;48980;48981	chr2:178570759;178570758;178570757	chr2:179435486;179435485;179435484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-134
• Domain position: 15
• Structural Position: 23
• Q(SASA): 0.292
• 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
A/S	rs764929320	-0.814	0.979	N	0.531	0.25	0.200317383148	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
A/S	rs764929320	-0.814	0.979	N	0.531	0.25	0.200317383148	gnomAD-4.0.0	1.5917E-06	None	None	None	None	I	None	0	0	None	0	2.77408E-05	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
A/C	0.687	likely_pathogenic	0.7347	pathogenic	-0.601	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/D	0.9135	likely_pathogenic	0.9373	pathogenic	-1.203	Destabilizing	0.998	D	0.694	prob.neutral	N	0.488902111	None	None	I
A/E	0.7999	likely_pathogenic	0.8532	pathogenic	-1.351	Destabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
A/F	0.8215	likely_pathogenic	0.8449	pathogenic	-1.171	Destabilizing	0.991	D	0.731	prob.delet.	None	None	None	None	I
A/G	0.3652	ambiguous	0.4237	ambiguous	-0.705	Destabilizing	0.979	D	0.541	neutral	N	0.518616161	None	None	I
A/H	0.8558	likely_pathogenic	0.8876	pathogenic	-0.88	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
A/I	0.6695	likely_pathogenic	0.6888	pathogenic	-0.516	Destabilizing	0.938	D	0.627	neutral	None	None	None	None	I
A/K	0.8297	likely_pathogenic	0.8789	pathogenic	-1.065	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	I
A/L	0.652	likely_pathogenic	0.6792	pathogenic	-0.516	Destabilizing	0.938	D	0.482	neutral	None	None	None	None	I
A/M	0.6398	likely_pathogenic	0.6546	pathogenic	-0.279	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
A/N	0.7944	likely_pathogenic	0.8259	pathogenic	-0.571	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
A/P	0.9166	likely_pathogenic	0.9247	pathogenic	-0.51	Destabilizing	0.998	D	0.699	prob.neutral	N	0.473898501	None	None	I
A/Q	0.7113	likely_pathogenic	0.7641	pathogenic	-0.911	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
A/R	0.7278	likely_pathogenic	0.7788	pathogenic	-0.498	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
A/S	0.1601	likely_benign	0.1723	benign	-0.701	Destabilizing	0.979	D	0.531	neutral	N	0.474151991	None	None	I
A/T	0.3444	ambiguous	0.329	benign	-0.79	Destabilizing	0.958	D	0.671	neutral	N	0.478013105	None	None	I
A/V	0.3522	ambiguous	0.3585	ambiguous	-0.51	Destabilizing	0.142	N	0.398	neutral	N	0.496110869	None	None	I
A/W	0.9684	likely_pathogenic	0.976	pathogenic	-1.353	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/Y	0.8966	likely_pathogenic	0.9181	pathogenic	-1.03	Destabilizing	0.995	D	0.738	prob.delet.	None	None	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.