TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29742	89449;89450;89451	chr2:178553781;178553780;178553779	chr2:179418508;179418507;179418506
N2AB	28101	84526;84527;84528	chr2:178553781;178553780;178553779	chr2:179418508;179418507;179418506
N2A	27174	81745;81746;81747	chr2:178553781;178553780;178553779	chr2:179418508;179418507;179418506
N2B	20677	62254;62255;62256	chr2:178553781;178553780;178553779	chr2:179418508;179418507;179418506
Novex-1	20802	62629;62630;62631	chr2:178553781;178553780;178553779	chr2:179418508;179418507;179418506
Novex-2	20869	62830;62831;62832	chr2:178553781;178553780;178553779	chr2:179418508;179418507;179418506
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-105
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.601
• 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
R/G	None	None	0.549	N	0.535	0.166	0.463586170655	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.4788	ambiguous	0.4197	ambiguous	-0.739	Destabilizing	0.25	N	0.477	neutral	None	None	None	None	N
R/C	0.203	likely_benign	0.1721	benign	-0.877	Destabilizing	0.992	D	0.567	neutral	None	None	None	None	N
R/D	0.7339	likely_pathogenic	0.6883	pathogenic	0.087	Stabilizing	0.617	D	0.564	neutral	None	None	None	None	N
R/E	0.461	ambiguous	0.409	ambiguous	0.224	Stabilizing	0.25	N	0.519	neutral	None	None	None	None	N
R/F	0.5121	ambiguous	0.4889	ambiguous	-0.572	Destabilizing	0.972	D	0.572	neutral	None	None	None	None	N
R/G	0.3653	ambiguous	0.3034	benign	-1.036	Destabilizing	0.549	D	0.535	neutral	N	0.517481511	None	None	N
R/H	0.0974	likely_benign	0.0943	benign	-1.203	Destabilizing	0.92	D	0.555	neutral	None	None	None	None	N
R/I	0.2719	likely_benign	0.2369	benign	0.057	Stabilizing	0.896	D	0.584	neutral	N	0.491084344	None	None	N
R/K	0.1123	likely_benign	0.1041	benign	-0.627	Destabilizing	0.002	N	0.169	neutral	N	0.425723356	None	None	N
R/L	0.301	likely_benign	0.2682	benign	0.057	Stabilizing	0.617	D	0.55	neutral	None	None	None	None	N
R/M	0.3066	likely_benign	0.2659	benign	-0.436	Destabilizing	0.972	D	0.567	neutral	None	None	None	None	N
R/N	0.5673	likely_pathogenic	0.5218	ambiguous	-0.329	Destabilizing	0.617	D	0.492	neutral	None	None	None	None	N
R/P	0.9245	likely_pathogenic	0.8878	pathogenic	-0.187	Destabilizing	0.92	D	0.573	neutral	None	None	None	None	N
R/Q	0.1159	likely_benign	0.1059	benign	-0.426	Destabilizing	0.447	N	0.535	neutral	None	None	None	None	N
R/S	0.4934	ambiguous	0.4316	ambiguous	-1.098	Destabilizing	0.045	N	0.321	neutral	N	0.450792372	None	None	N
R/T	0.2448	likely_benign	0.2134	benign	-0.773	Destabilizing	0.379	N	0.508	neutral	N	0.441172811	None	None	N
R/V	0.3405	ambiguous	0.3057	benign	-0.187	Destabilizing	0.617	D	0.581	neutral	None	None	None	None	N
R/W	0.215	likely_benign	0.1902	benign	-0.264	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	N
R/Y	0.3982	ambiguous	0.3678	ambiguous	0.03	Stabilizing	0.972	D	0.585	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.