TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6775	20548;20549;20550	chr2:178725999;178725998;178725997	chr2:179590726;179590725;179590724
N2AB	6458	19597;19598;19599	chr2:178725999;178725998;178725997	chr2:179590726;179590725;179590724
N2A	5531	16816;16817;16818	chr2:178725999;178725998;178725997	chr2:179590726;179590725;179590724
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-52
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.6186
• 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	None	None	0.042	N	0.42	0.091	0.158396225186	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
N/A	0.196	likely_benign	0.1773	benign	-0.255	Destabilizing	0.055	N	0.48	neutral	None	None	None	None	N
N/C	0.3713	ambiguous	0.3319	benign	0.384	Stabilizing	0.958	D	0.588	neutral	None	None	None	None	N
N/D	0.1123	likely_benign	0.1169	benign	0.049	Stabilizing	None	N	0.179	neutral	N	0.430431035	None	None	N
N/E	0.2967	likely_benign	0.3136	benign	-0.001	Destabilizing	0.055	N	0.352	neutral	None	None	None	None	N
N/F	0.4609	ambiguous	0.438	ambiguous	-0.686	Destabilizing	0.859	D	0.603	neutral	None	None	None	None	N
N/G	0.1264	likely_benign	0.1348	benign	-0.403	Destabilizing	None	N	0.163	neutral	None	None	None	None	N
N/H	0.1281	likely_benign	0.1173	benign	-0.448	Destabilizing	0.822	D	0.446	neutral	N	0.507315738	None	None	N
N/I	0.2827	likely_benign	0.2568	benign	0.044	Stabilizing	0.602	D	0.592	neutral	N	0.491822076	None	None	N
N/K	0.2683	likely_benign	0.2764	benign	0.128	Stabilizing	0.175	N	0.345	neutral	N	0.469354782	None	None	N
N/L	0.2758	likely_benign	0.2481	benign	0.044	Stabilizing	0.364	N	0.587	neutral	None	None	None	None	N
N/M	0.3171	likely_benign	0.2827	benign	0.38	Stabilizing	0.958	D	0.569	neutral	None	None	None	None	N
N/P	0.6736	likely_pathogenic	0.68	pathogenic	-0.03	Destabilizing	0.667	D	0.556	neutral	None	None	None	None	N
N/Q	0.2996	likely_benign	0.2792	benign	-0.281	Destabilizing	0.667	D	0.4	neutral	None	None	None	None	N
N/R	0.3478	ambiguous	0.3645	ambiguous	0.213	Stabilizing	0.364	N	0.402	neutral	None	None	None	None	N
N/S	0.0953	likely_benign	0.089	benign	-0.026	Destabilizing	0.042	N	0.42	neutral	N	0.473664524	None	None	N
N/T	0.1383	likely_benign	0.124	benign	0.053	Stabilizing	0.175	N	0.329	neutral	N	0.50229392	None	None	N
N/V	0.2762	likely_benign	0.2565	benign	-0.03	Destabilizing	0.364	N	0.587	neutral	None	None	None	None	N
N/W	0.7147	likely_pathogenic	0.7149	pathogenic	-0.707	Destabilizing	0.958	D	0.599	neutral	None	None	None	None	N
N/Y	0.1363	likely_benign	0.1341	benign	-0.429	Destabilizing	0.822	D	0.573	neutral	N	0.491822076	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.