TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34368	103327;103328;103329	chr2:178533513;178533512;178533511	chr2:179398240;179398239;179398238
N2AB	32727	98404;98405;98406	chr2:178533513;178533512;178533511	chr2:179398240;179398239;179398238
N2A	31800	95623;95624;95625	chr2:178533513;178533512;178533511	chr2:179398240;179398239;179398238
N2B	25303	76132;76133;76134	chr2:178533513;178533512;178533511	chr2:179398240;179398239;179398238
Novex-1	25428	76507;76508;76509	chr2:178533513;178533512;178533511	chr2:179398240;179398239;179398238
Novex-2	25495	76708;76709;76710	chr2:178533513;178533512;178533511	chr2:179398240;179398239;179398238
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-162
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5014
• 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
L/S	None	None	0.997	N	0.804	0.555	0.834087401315	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.9314	likely_pathogenic	0.8651	pathogenic	-1.033	Destabilizing	0.991	D	0.69	prob.neutral	None	None	None	None	I
L/C	0.9781	likely_pathogenic	0.9555	pathogenic	-0.771	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
L/D	0.9961	likely_pathogenic	0.9897	pathogenic	-0.118	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	I
L/E	0.9771	likely_pathogenic	0.9477	pathogenic	-0.113	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
L/F	0.8286	likely_pathogenic	0.6888	pathogenic	-0.57	Destabilizing	0.235	N	0.323	neutral	N	0.495082733	None	None	I
L/G	0.9818	likely_pathogenic	0.9584	pathogenic	-1.322	Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	I
L/H	0.9489	likely_pathogenic	0.8834	pathogenic	-0.408	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
L/I	0.5645	likely_pathogenic	0.4488	ambiguous	-0.336	Destabilizing	0.955	D	0.471	neutral	N	0.478209126	None	None	I
L/K	0.9061	likely_pathogenic	0.8406	pathogenic	-0.566	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
L/M	0.5465	ambiguous	0.4366	ambiguous	-0.483	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	I
L/N	0.967	likely_pathogenic	0.9322	pathogenic	-0.463	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	I
L/P	0.9238	likely_pathogenic	0.8266	pathogenic	-0.535	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	I
L/Q	0.9062	likely_pathogenic	0.8102	pathogenic	-0.558	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
L/R	0.8952	likely_pathogenic	0.7984	pathogenic	-0.103	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
L/S	0.9791	likely_pathogenic	0.947	pathogenic	-1.087	Destabilizing	0.997	D	0.804	deleterious	N	0.443229761	None	None	I
L/T	0.9406	likely_pathogenic	0.8853	pathogenic	-0.954	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	I
L/V	0.6438	likely_pathogenic	0.5022	ambiguous	-0.535	Destabilizing	0.977	D	0.532	neutral	N	0.44921437	None	None	I
L/W	0.9518	likely_pathogenic	0.8869	pathogenic	-0.615	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
L/Y	0.9512	likely_pathogenic	0.9035	pathogenic	-0.374	Destabilizing	0.99	D	0.817	deleterious	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.