TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13798	41617;41618;41619	chr2:178636179;178636178;178636177	chr2:179500906;179500905;179500904
N2AB	12157	36694;36695;36696	chr2:178636179;178636178;178636177	chr2:179500906;179500905;179500904
N2A	11230	33913;33914;33915	chr2:178636179;178636178;178636177	chr2:179500906;179500905;179500904
N2B	4733	14422;14423;14424	chr2:178636179;178636178;178636177	chr2:179500906;179500905;179500904
Novex-1	4858	14797;14798;14799	chr2:178636179;178636178;178636177	chr2:179500906;179500905;179500904
Novex-2	4925	14998;14999;15000	chr2:178636179;178636178;178636177	chr2:179500906;179500905;179500904
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-88
• Domain position: 19
• Structural Position: 28
• Q(SASA): 0.1395
• 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/S	rs779304267	-2.978	0.876	N	0.697	0.266	0.438383285633	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
L/S	rs779304267	-2.978	0.876	N	0.697	0.266	0.438383285633	gnomAD-4.0.0	1.59522E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86467E-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	0.7697	likely_pathogenic	0.8227	pathogenic	-2.451	Highly Destabilizing	0.842	D	0.676	prob.neutral	None	None	None	None	N
L/C	0.7952	likely_pathogenic	0.7954	pathogenic	-1.608	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
L/D	0.9987	likely_pathogenic	0.999	pathogenic	-2.776	Highly Destabilizing	0.974	D	0.821	deleterious	None	None	None	None	N
L/E	0.9914	likely_pathogenic	0.9942	pathogenic	-2.548	Highly Destabilizing	0.974	D	0.804	deleterious	None	None	None	None	N
L/F	0.6111	likely_pathogenic	0.6504	pathogenic	-1.441	Destabilizing	0.028	N	0.502	neutral	N	0.324631385	None	None	N
L/G	0.9751	likely_pathogenic	0.9787	pathogenic	-2.994	Highly Destabilizing	0.974	D	0.759	deleterious	None	None	None	None	N
L/H	0.973	likely_pathogenic	0.9796	pathogenic	-2.42	Highly Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
L/I	0.2413	likely_benign	0.2782	benign	-0.883	Destabilizing	0.067	N	0.412	neutral	None	None	None	None	N
L/K	0.986	likely_pathogenic	0.9882	pathogenic	-1.966	Destabilizing	0.974	D	0.705	prob.delet.	None	None	None	None	N
L/M	0.2971	likely_benign	0.3118	benign	-0.741	Destabilizing	0.454	N	0.595	neutral	N	0.345823763	None	None	N
L/N	0.9883	likely_pathogenic	0.9902	pathogenic	-2.292	Highly Destabilizing	0.974	D	0.828	deleterious	None	None	None	None	N
L/P	0.9957	likely_pathogenic	0.9966	pathogenic	-1.386	Destabilizing	0.991	D	0.827	deleterious	None	None	None	None	N
L/Q	0.9523	likely_pathogenic	0.9638	pathogenic	-2.161	Highly Destabilizing	0.974	D	0.727	deleterious	None	None	None	None	N
L/R	0.9642	likely_pathogenic	0.9721	pathogenic	-1.663	Destabilizing	0.974	D	0.745	deleterious	None	None	None	None	N
L/S	0.9534	likely_pathogenic	0.969	pathogenic	-2.966	Highly Destabilizing	0.876	D	0.697	prob.delet.	N	0.36038844	None	None	N
L/T	0.8566	likely_pathogenic	0.8825	pathogenic	-2.592	Highly Destabilizing	0.142	N	0.443	neutral	None	None	None	None	N
L/V	0.211	likely_benign	0.2373	benign	-1.386	Destabilizing	0.051	N	0.346	neutral	N	0.343635135	None	None	N
L/W	0.967	likely_pathogenic	0.9743	pathogenic	-1.848	Destabilizing	0.997	D	0.739	deleterious	N	0.416962291	None	None	N
L/Y	0.9547	likely_pathogenic	0.962	pathogenic	-1.536	Destabilizing	0.904	D	0.744	deleterious	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.