TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3904	11935;11936;11937	chr2:178741523;178741522;178741521	chr2:179606250;179606249;179606248
N2AB	3587	10984;10985;10986	chr2:178741523;178741522;178741521	chr2:179606250;179606249;179606248
N2A	None	None	chr2:None	chr2:None
N2B	3541	10846;10847;10848	chr2:178741523;178741522;178741521	chr2:179606250;179606249;179606248
Novex-1	3666	11221;11222;11223	chr2:178741523;178741522;178741521	chr2:179606250;179606249;179606248
Novex-2	3733	11422;11423;11424	chr2:178741523;178741522;178741521	chr2:179606250;179606249;179606248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-27
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3778
• 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
S/R	None	None	0.062	N	0.561	0.331	None	gnomAD-4.0.0	1.59114E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85791E-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
S/A	0.1278	likely_benign	0.1232	benign	-0.481	Destabilizing	0.035	N	0.444	neutral	None	None	None	None	I
S/C	0.1724	likely_benign	0.1616	benign	-0.358	Destabilizing	0.78	D	0.561	neutral	D	0.69984569	None	None	I
S/D	0.5533	ambiguous	0.5102	ambiguous	-0.46	Destabilizing	0.081	N	0.543	neutral	None	None	None	None	I
S/E	0.6243	likely_pathogenic	0.5957	pathogenic	-0.542	Destabilizing	0.149	N	0.529	neutral	None	None	None	None	I
S/F	0.3293	likely_benign	0.2996	benign	-0.98	Destabilizing	0.555	D	0.661	neutral	None	None	None	None	I
S/G	0.1481	likely_benign	0.133	benign	-0.623	Destabilizing	0.027	N	0.511	neutral	D	0.571490123	None	None	I
S/H	0.3714	ambiguous	0.322	benign	-1.194	Destabilizing	0.38	N	0.583	neutral	None	None	None	None	I
S/I	0.3238	likely_benign	0.301	benign	-0.229	Destabilizing	0.188	N	0.667	neutral	D	0.55910946	None	None	I
S/K	0.6108	likely_pathogenic	0.5284	ambiguous	-0.697	Destabilizing	0.002	N	0.247	neutral	None	None	None	None	I
S/L	0.1801	likely_benign	0.1688	benign	-0.229	Destabilizing	0.081	N	0.634	neutral	None	None	None	None	I
S/M	0.3577	ambiguous	0.3242	benign	0.182	Stabilizing	0.555	D	0.582	neutral	None	None	None	None	I
S/N	0.1941	likely_benign	0.161	benign	-0.484	Destabilizing	None	N	0.254	neutral	N	0.515456717	None	None	I
S/P	0.6508	likely_pathogenic	0.6567	pathogenic	-0.283	Destabilizing	0.555	D	0.597	neutral	None	None	None	None	I
S/Q	0.5639	ambiguous	0.5023	ambiguous	-0.816	Destabilizing	0.38	N	0.562	neutral	None	None	None	None	I
S/R	0.4621	ambiguous	0.3873	ambiguous	-0.408	Destabilizing	0.062	N	0.561	neutral	N	0.51270812	None	None	I
S/T	0.0976	likely_benign	0.0894	benign	-0.534	Destabilizing	None	N	0.231	neutral	N	0.49424768	None	None	I
S/V	0.3257	likely_benign	0.304	benign	-0.283	Destabilizing	0.081	N	0.625	neutral	None	None	None	None	I
S/W	0.5062	ambiguous	0.4797	ambiguous	-0.954	Destabilizing	0.935	D	0.712	prob.delet.	None	None	None	None	I
S/Y	0.2664	likely_benign	0.2489	benign	-0.696	Destabilizing	0.555	D	0.665	neutral	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.