TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8879	26860;26861;26862	chr2:178714023;178714022;178714021	chr2:179578750;179578749;179578748
N2AB	8562	25909;25910;25911	chr2:178714023;178714022;178714021	chr2:179578750;179578749;179578748
N2A	7635	23128;23129;23130	chr2:178714023;178714022;178714021	chr2:179578750;179578749;179578748
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-74
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3292
• 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/G	None	None	0.939	N	0.431	0.328	0.350524144436	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-06	0	0
S/I	None	None	0.982	N	0.655	0.393	0.743059446457	gnomAD-4.0.0	6.84317E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99552E-07	0	0
S/N	None	None	0.939	D	0.482	0.25	0.307332253619	gnomAD-4.0.0	6.84317E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99552E-07	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
S/A	0.1252	likely_benign	0.1417	benign	-0.477	Destabilizing	0.807	D	0.351	neutral	None	None	None	None	N
S/C	0.2133	likely_benign	0.2871	benign	-0.301	Destabilizing	0.999	D	0.596	neutral	N	0.510219501	None	None	N
S/D	0.7541	likely_pathogenic	0.7897	pathogenic	0.363	Stabilizing	0.953	D	0.459	neutral	None	None	None	None	N
S/E	0.8584	likely_pathogenic	0.8709	pathogenic	0.295	Stabilizing	0.953	D	0.469	neutral	None	None	None	None	N
S/F	0.2582	likely_benign	0.3297	benign	-0.916	Destabilizing	0.993	D	0.675	prob.neutral	None	None	None	None	N
S/G	0.1824	likely_benign	0.2064	benign	-0.635	Destabilizing	0.939	D	0.431	neutral	N	0.486581837	None	None	N
S/H	0.5529	ambiguous	0.5794	pathogenic	-1.096	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
S/I	0.2641	likely_benign	0.3208	benign	-0.186	Destabilizing	0.982	D	0.655	neutral	N	0.519668959	None	None	N
S/K	0.925	likely_pathogenic	0.9332	pathogenic	-0.468	Destabilizing	0.953	D	0.463	neutral	None	None	None	None	N
S/L	0.1382	likely_benign	0.1815	benign	-0.186	Destabilizing	0.91	D	0.523	neutral	None	None	None	None	N
S/M	0.2938	likely_benign	0.3394	benign	0.021	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	N
S/N	0.3041	likely_benign	0.3505	ambiguous	-0.228	Destabilizing	0.939	D	0.482	neutral	D	0.523285268	None	None	N
S/P	0.8317	likely_pathogenic	0.9068	pathogenic	-0.252	Destabilizing	0.993	D	0.613	neutral	None	None	None	None	N
S/Q	0.7674	likely_pathogenic	0.7781	pathogenic	-0.433	Destabilizing	0.993	D	0.58	neutral	None	None	None	None	N
S/R	0.8493	likely_pathogenic	0.8602	pathogenic	-0.305	Destabilizing	0.982	D	0.624	neutral	N	0.492693002	None	None	N
S/T	0.0947	likely_benign	0.0964	benign	-0.353	Destabilizing	0.079	N	0.179	neutral	N	0.444707054	None	None	N
S/V	0.2609	likely_benign	0.3127	benign	-0.252	Destabilizing	0.91	D	0.509	neutral	None	None	None	None	N
S/W	0.4462	ambiguous	0.5395	ambiguous	-0.894	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
S/Y	0.2332	likely_benign	0.2971	benign	-0.627	Destabilizing	0.998	D	0.665	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.