TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8753	26482;26483;26484	chr2:178714517;178714516;178714515	chr2:179579244;179579243;179579242
N2AB	8436	25531;25532;25533	chr2:178714517;178714516;178714515	chr2:179579244;179579243;179579242
N2A	7509	22750;22751;22752	chr2:178714517;178714516;178714515	chr2:179579244;179579243;179579242
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-73
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.3655
• 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
V/G	rs867579263	None	0.285	N	0.727	0.307	0.711079051923	gnomAD-4.0.0	5.4756E-06	None	None	None	None	I	None	8.97022E-05	0	None	0	0	None	0	1.73611E-04	2.6989E-06	0	1.65733E-05
V/I	rs373070956	-0.328	None	N	0.335	0.13	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs373070956	-0.328	None	N	0.335	0.13	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs373070956	-0.328	None	N	0.335	0.13	None	gnomAD-4.0.0	6.57367E-06	None	None	None	None	I	None	2.41336E-05	0	None	0	0	None	0	0	0	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
V/A	0.1004	likely_benign	0.1145	benign	-1.834	Destabilizing	None	N	0.204	neutral	N	0.465580106	None	None	I
V/C	0.6204	likely_pathogenic	0.7058	pathogenic	-1.476	Destabilizing	0.895	D	0.685	prob.neutral	None	None	None	None	I
V/D	0.4639	ambiguous	0.5637	ambiguous	-1.633	Destabilizing	0.984	D	0.779	deleterious	N	0.518926238	None	None	I
V/E	0.4158	ambiguous	0.4895	ambiguous	-1.483	Destabilizing	0.932	D	0.752	deleterious	None	None	None	None	I
V/F	0.1365	likely_benign	0.1839	benign	-1.068	Destabilizing	0.799	D	0.729	prob.delet.	N	0.461446694	None	None	I
V/G	0.1443	likely_benign	0.1699	benign	-2.316	Highly Destabilizing	0.285	N	0.727	prob.delet.	N	0.488958698	None	None	I
V/H	0.6626	likely_pathogenic	0.7473	pathogenic	-1.745	Destabilizing	0.972	D	0.762	deleterious	None	None	None	None	I
V/I	0.0723	likely_benign	0.0767	benign	-0.537	Destabilizing	None	N	0.335	neutral	N	0.512219259	None	None	I
V/K	0.4862	ambiguous	0.5772	pathogenic	-1.508	Destabilizing	0.967	D	0.756	deleterious	None	None	None	None	I
V/L	0.1588	likely_benign	0.1913	benign	-0.537	Destabilizing	0.019	N	0.475	neutral	N	0.50194355	None	None	I
V/M	0.114	likely_benign	0.1315	benign	-0.604	Destabilizing	0.791	D	0.565	neutral	None	None	None	None	I
V/N	0.3314	likely_benign	0.4179	ambiguous	-1.597	Destabilizing	0.899	D	0.78	deleterious	None	None	None	None	I
V/P	0.7399	likely_pathogenic	0.7892	pathogenic	-0.937	Destabilizing	0.815	D	0.76	deleterious	None	None	None	None	I
V/Q	0.4395	ambiguous	0.5205	ambiguous	-1.542	Destabilizing	0.977	D	0.749	deleterious	None	None	None	None	I
V/R	0.454	ambiguous	0.5463	ambiguous	-1.202	Destabilizing	0.984	D	0.783	deleterious	None	None	None	None	I
V/S	0.1863	likely_benign	0.2313	benign	-2.304	Highly Destabilizing	0.137	N	0.707	prob.neutral	None	None	None	None	I
V/T	0.1443	likely_benign	0.1701	benign	-2.002	Highly Destabilizing	0.06	N	0.571	neutral	None	None	None	None	I
V/W	0.7505	likely_pathogenic	0.844	pathogenic	-1.358	Destabilizing	0.992	D	0.736	prob.delet.	None	None	None	None	I
V/Y	0.4927	ambiguous	0.594	pathogenic	-1.025	Destabilizing	0.806	D	0.715	prob.delet.	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.