TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24919	74980;74981;74982	chr2:178571377;178571376;178571375	chr2:179436104;179436103;179436102
N2AB	23278	70057;70058;70059	chr2:178571377;178571376;178571375	chr2:179436104;179436103;179436102
N2A	22351	67276;67277;67278	chr2:178571377;178571376;178571375	chr2:179436104;179436103;179436102
N2B	15854	47785;47786;47787	chr2:178571377;178571376;178571375	chr2:179436104;179436103;179436102
Novex-1	15979	48160;48161;48162	chr2:178571377;178571376;178571375	chr2:179436104;179436103;179436102
Novex-2	16046	48361;48362;48363	chr2:178571377;178571376;178571375	chr2:179436104;179436103;179436102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-69
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.8022
• 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
L/V	None	None	0.004	N	0.163	0.067	0.199424873507	gnomAD-4.0.0	3.60099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93753E-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
L/A	0.0595	likely_benign	0.0622	benign	-0.603	Destabilizing	None	N	0.083	neutral	None	None	None	None	N
L/C	0.1422	likely_benign	0.1395	benign	-0.68	Destabilizing	0.54	D	0.215	neutral	None	None	None	None	N
L/D	0.2098	likely_benign	0.1885	benign	0.137	Stabilizing	0.033	N	0.322	neutral	None	None	None	None	N
L/E	0.1421	likely_benign	0.1348	benign	0.056	Stabilizing	None	N	0.187	neutral	None	None	None	None	N
L/F	0.0555	likely_benign	0.0532	benign	-0.532	Destabilizing	0.001	N	0.134	neutral	None	None	None	None	N
L/G	0.1486	likely_benign	0.1458	benign	-0.774	Destabilizing	0.033	N	0.322	neutral	None	None	None	None	N
L/H	0.0626	likely_benign	0.0643	benign	-0.029	Destabilizing	None	N	0.191	neutral	None	None	None	None	N
L/I	0.0566	likely_benign	0.0556	benign	-0.277	Destabilizing	0.001	N	0.109	neutral	None	None	None	None	N
L/K	0.0966	likely_benign	0.1017	benign	-0.269	Destabilizing	0.033	N	0.297	neutral	None	None	None	None	N
L/M	0.0647	likely_benign	0.0684	benign	-0.374	Destabilizing	0.304	N	0.233	neutral	N	0.443829114	None	None	N
L/N	0.0855	likely_benign	0.087	benign	-0.1	Destabilizing	0.001	N	0.201	neutral	None	None	None	None	N
L/P	0.6364	likely_pathogenic	0.5466	ambiguous	-0.352	Destabilizing	0.202	N	0.407	neutral	N	0.434630841	None	None	N
L/Q	0.0646	likely_benign	0.0678	benign	-0.295	Destabilizing	0.059	N	0.37	neutral	N	0.414506285	None	None	N
L/R	0.0759	likely_benign	0.0774	benign	0.237	Stabilizing	0.111	N	0.399	neutral	N	0.383530017	None	None	N
L/S	0.0643	likely_benign	0.0652	benign	-0.621	Destabilizing	0.003	N	0.1	neutral	None	None	None	None	N
L/T	0.0638	likely_benign	0.0647	benign	-0.589	Destabilizing	None	N	0.091	neutral	None	None	None	None	N
L/V	0.0512	likely_benign	0.0509	benign	-0.352	Destabilizing	0.004	N	0.163	neutral	N	0.407772314	None	None	N
L/W	0.1129	likely_benign	0.1035	benign	-0.533	Destabilizing	0.931	D	0.247	neutral	None	None	None	None	N
L/Y	0.1024	likely_benign	0.098	benign	-0.287	Destabilizing	0.076	N	0.319	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.