TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4817	14674;14675;14676	chr2:178735997;178735996;178735995	chr2:179600724;179600723;179600722
N2AB	4500	13723;13724;13725	chr2:178735997;178735996;178735995	chr2:179600724;179600723;179600722
N2A	3573	10942;10943;10944	chr2:178735997;178735996;178735995	chr2:179600724;179600723;179600722
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-31
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2187
• 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/I	rs1299461448	-0.087	0.669	N	0.481	0.34	0.436455679973	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/I	rs1299461448	-0.087	0.669	N	0.481	0.34	0.436455679973	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1299461448	-0.087	0.669	N	0.481	0.34	0.436455679973	gnomAD-4.0.0	2.56314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78819E-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
T/A	0.1076	likely_benign	0.0934	benign	-0.944	Destabilizing	0.454	N	0.337	neutral	N	0.490434602	None	None	N
T/C	0.537	ambiguous	0.4757	ambiguous	-0.751	Destabilizing	0.998	D	0.501	neutral	None	None	None	None	N
T/D	0.5324	ambiguous	0.4594	ambiguous	-1.495	Destabilizing	0.728	D	0.483	neutral	None	None	None	None	N
T/E	0.3806	ambiguous	0.3358	benign	-1.392	Destabilizing	0.067	N	0.283	neutral	None	None	None	None	N
T/F	0.3075	likely_benign	0.2608	benign	-0.816	Destabilizing	0.974	D	0.561	neutral	None	None	None	None	N
T/G	0.3771	ambiguous	0.3115	benign	-1.288	Destabilizing	0.728	D	0.519	neutral	None	None	None	None	N
T/H	0.3073	likely_benign	0.2728	benign	-1.581	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	N
T/I	0.2233	likely_benign	0.1944	benign	-0.081	Destabilizing	0.669	D	0.481	neutral	N	0.470626642	None	None	N
T/K	0.2833	likely_benign	0.2452	benign	-0.8	Destabilizing	0.801	D	0.478	neutral	N	0.463548433	None	None	N
T/L	0.1374	likely_benign	0.1167	benign	-0.081	Destabilizing	0.525	D	0.458	neutral	None	None	None	None	N
T/M	0.0999	likely_benign	0.0944	benign	0.191	Stabilizing	0.974	D	0.515	neutral	None	None	None	None	N
T/N	0.1779	likely_benign	0.1531	benign	-1.232	Destabilizing	0.842	D	0.473	neutral	None	None	None	None	N
T/P	0.4673	ambiguous	0.3521	ambiguous	-0.336	Destabilizing	0.966	D	0.521	neutral	N	0.504591376	None	None	N
T/Q	0.2798	likely_benign	0.2528	benign	-1.251	Destabilizing	0.949	D	0.533	neutral	None	None	None	None	N
T/R	0.2111	likely_benign	0.1803	benign	-0.749	Destabilizing	0.934	D	0.533	neutral	N	0.453540635	None	None	N
T/S	0.1349	likely_benign	0.1152	benign	-1.369	Destabilizing	0.022	N	0.169	neutral	N	0.467053332	None	None	N
T/V	0.1724	likely_benign	0.1478	benign	-0.336	Destabilizing	0.029	N	0.162	neutral	None	None	None	None	N
T/W	0.6805	likely_pathogenic	0.6307	pathogenic	-0.914	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	N
T/Y	0.3716	ambiguous	0.3094	benign	-0.581	Destabilizing	0.991	D	0.566	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.