TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7008	21247;21248;21249	chr2:178724353;178724352;178724351	chr2:179589080;179589079;179589078
N2AB	6691	20296;20297;20298	chr2:178724353;178724352;178724351	chr2:179589080;179589079;179589078
N2A	5764	17515;17516;17517	chr2:178724353;178724352;178724351	chr2:179589080;179589079;179589078
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-54
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2094
• 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
L/F	rs770243060	None	0.81	N	0.389	0.133	0.560341545759	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	1.09649E-03	0	0	None	0	0	0	0	0
L/F	rs770243060	None	0.81	N	0.389	0.133	0.560341545759	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	0
L/I	rs770243060	-1.242	0.002	N	0.066	0.125	0.435699915968	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.67094E-04	None	0	None	0	0	0
L/I	rs770243060	-1.242	0.002	N	0.066	0.125	0.435699915968	gnomAD-4.0.0	4.10588E-06	None	None	None	None	N	None	0	0	None	0	7.5601E-05	None	0	0	2.69875E-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
L/A	0.18	likely_benign	0.1447	benign	-1.586	Destabilizing	0.4	N	0.389	neutral	None	None	None	None	N
L/C	0.4611	ambiguous	0.4009	ambiguous	-1.023	Destabilizing	0.992	D	0.417	neutral	None	None	None	None	N
L/D	0.4621	ambiguous	0.3718	ambiguous	-0.855	Destabilizing	0.739	D	0.523	neutral	None	None	None	None	N
L/E	0.2674	likely_benign	0.2243	benign	-0.862	Destabilizing	0.85	D	0.517	neutral	None	None	None	None	N
L/F	0.1059	likely_benign	0.086	benign	-1.128	Destabilizing	0.81	D	0.389	neutral	N	0.467277269	None	None	N
L/G	0.3535	ambiguous	0.2968	benign	-1.904	Destabilizing	0.617	D	0.513	neutral	None	None	None	None	N
L/H	0.1623	likely_benign	0.1424	benign	-1.059	Destabilizing	0.97	D	0.522	neutral	N	0.45588684	None	None	N
L/I	0.0778	likely_benign	0.0666	benign	-0.791	Destabilizing	0.002	N	0.066	neutral	N	0.470778934	None	None	N
L/K	0.2394	likely_benign	0.2068	benign	-1.016	Destabilizing	0.85	D	0.474	neutral	None	None	None	None	N
L/M	0.1158	likely_benign	0.0965	benign	-0.591	Destabilizing	0.059	N	0.228	neutral	None	None	None	None	N
L/N	0.2025	likely_benign	0.1703	benign	-0.81	Destabilizing	0.048	N	0.402	neutral	None	None	None	None	N
L/P	0.1743	likely_benign	0.1576	benign	-1.024	Destabilizing	0.963	D	0.557	neutral	N	0.43955195	None	None	N
L/Q	0.1248	likely_benign	0.1105	benign	-1.001	Destabilizing	0.92	D	0.526	neutral	None	None	None	None	N
L/R	0.1615	likely_benign	0.1429	benign	-0.414	Destabilizing	0.896	D	0.512	neutral	N	0.422350269	None	None	N
L/S	0.1561	likely_benign	0.1248	benign	-1.477	Destabilizing	0.617	D	0.46	neutral	None	None	None	None	N
L/T	0.1511	likely_benign	0.1219	benign	-1.363	Destabilizing	0.617	D	0.354	neutral	None	None	None	None	N
L/V	0.09	likely_benign	0.0741	benign	-1.024	Destabilizing	0.016	N	0.106	neutral	N	0.467103911	None	None	N
L/W	0.2276	likely_benign	0.1883	benign	-1.159	Destabilizing	0.992	D	0.539	neutral	None	None	None	None	N
L/Y	0.2822	likely_benign	0.2288	benign	-0.943	Destabilizing	0.92	D	0.445	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.