TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7104	21535;21536;21537	chr2:178723949;178723948;178723947	chr2:179588676;179588675;179588674
N2AB	6787	20584;20585;20586	chr2:178723949;178723948;178723947	chr2:179588676;179588675;179588674
N2A	5860	17803;17804;17805	chr2:178723949;178723948;178723947	chr2:179588676;179588675;179588674
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-55
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.4011
• 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
N/S	rs1684986089	None	0.029	N	0.095	0.144	0.124217242631	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.77555E-04
N/S	rs1684986089	None	0.029	N	0.095	0.144	0.124217242631	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.77555E-04

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
N/A	0.183	likely_benign	0.1747	benign	-0.576	Destabilizing	0.329	N	0.368	neutral	None	None	None	None	N
N/C	0.2745	likely_benign	0.2642	benign	0.185	Stabilizing	0.017	N	0.341	neutral	None	None	None	None	N
N/D	0.1249	likely_benign	0.1222	benign	-0.611	Destabilizing	0.425	N	0.251	neutral	N	0.510334613	None	None	N
N/E	0.2941	likely_benign	0.2779	benign	-0.619	Destabilizing	0.329	N	0.219	neutral	None	None	None	None	N
N/F	0.3656	ambiguous	0.354	ambiguous	-0.919	Destabilizing	0.981	D	0.435	neutral	None	None	None	None	N
N/G	0.2326	likely_benign	0.2248	benign	-0.772	Destabilizing	0.495	N	0.241	neutral	None	None	None	None	N
N/H	0.0788	likely_benign	0.0775	benign	-0.835	Destabilizing	0.927	D	0.373	neutral	N	0.51172148	None	None	N
N/I	0.1575	likely_benign	0.1557	benign	-0.13	Destabilizing	0.927	D	0.458	neutral	N	0.518628809	None	None	N
N/K	0.1986	likely_benign	0.1911	benign	0.089	Stabilizing	0.023	N	0.09	neutral	N	0.47435517	None	None	N
N/L	0.1731	likely_benign	0.1699	benign	-0.13	Destabilizing	0.704	D	0.433	neutral	None	None	None	None	N
N/M	0.2851	likely_benign	0.2767	benign	0.555	Stabilizing	0.944	D	0.407	neutral	None	None	None	None	N
N/P	0.4447	ambiguous	0.4211	ambiguous	-0.253	Destabilizing	0.007	N	0.241	neutral	None	None	None	None	N
N/Q	0.2256	likely_benign	0.2182	benign	-0.673	Destabilizing	0.031	N	0.192	neutral	None	None	None	None	N
N/R	0.2013	likely_benign	0.1951	benign	0.26	Stabilizing	0.543	D	0.211	neutral	None	None	None	None	N
N/S	0.0801	likely_benign	0.0788	benign	-0.323	Destabilizing	0.029	N	0.095	neutral	N	0.426062578	None	None	N
N/T	0.1181	likely_benign	0.1119	benign	-0.185	Destabilizing	0.27	N	0.225	neutral	N	0.49425044	None	None	N
N/V	0.185	likely_benign	0.1797	benign	-0.253	Destabilizing	0.704	D	0.447	neutral	None	None	None	None	N
N/W	0.638	likely_pathogenic	0.6207	pathogenic	-0.778	Destabilizing	0.995	D	0.451	neutral	None	None	None	None	N
N/Y	0.1148	likely_benign	0.1132	benign	-0.505	Destabilizing	0.975	D	0.423	neutral	D	0.52366927	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.