TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14957	45094;45095;45096	chr2:178622714;178622713;178622712	chr2:179487441;179487440;179487439
N2AB	13316	40171;40172;40173	chr2:178622714;178622713;178622712	chr2:179487441;179487440;179487439
N2A	12389	37390;37391;37392	chr2:178622714;178622713;178622712	chr2:179487441;179487440;179487439
N2B	5892	17899;17900;17901	chr2:178622714;178622713;178622712	chr2:179487441;179487440;179487439
Novex-1	6017	18274;18275;18276	chr2:178622714;178622713;178622712	chr2:179487441;179487440;179487439
Novex-2	6084	18475;18476;18477	chr2:178622714;178622713;178622712	chr2:179487441;179487440;179487439
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-101
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2938
• 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
E/D	rs1489415457	-0.689	0.946	N	0.432	0.185	0.313518423057	gnomAD-2.1.1	4.14E-06	None	None	None	None	I	None	0	2.96E-05	None	0	0	None	0	None	0	0	0
E/D	rs1489415457	-0.689	0.946	N	0.432	0.185	0.313518423057	gnomAD-4.0.0	1.60617E-06	None	None	None	None	I	None	0	2.31342E-05	None	0	0	None	0	0	0	0	0
E/G	rs796961766	-0.967	0.811	N	0.49	0.18	0.283761946502	gnomAD-2.1.1	8.28E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.82E-05	0
E/G	rs796961766	-0.967	0.811	N	0.49	0.18	0.283761946502	gnomAD-4.0.0	2.95411E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.60657E-05	0	4.99484E-05

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
E/A	0.3326	likely_benign	0.3428	ambiguous	-0.688	Destabilizing	0.026	N	0.284	neutral	N	0.463817076	None	None	I
E/C	0.967	likely_pathogenic	0.9709	pathogenic	-0.33	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
E/D	0.1688	likely_benign	0.1867	benign	-0.732	Destabilizing	0.946	D	0.432	neutral	N	0.455881714	None	None	I
E/F	0.9364	likely_pathogenic	0.9411	pathogenic	-0.392	Destabilizing	0.952	D	0.637	neutral	None	None	None	None	I
E/G	0.2677	likely_benign	0.2715	benign	-0.969	Destabilizing	0.811	D	0.49	neutral	N	0.458348596	None	None	I
E/H	0.7982	likely_pathogenic	0.8207	pathogenic	-0.497	Destabilizing	0.976	D	0.381	neutral	None	None	None	None	I
E/I	0.8266	likely_pathogenic	0.8149	pathogenic	0.049	Stabilizing	0.976	D	0.644	neutral	None	None	None	None	I
E/K	0.4146	ambiguous	0.4165	ambiguous	-0.406	Destabilizing	0.896	D	0.424	neutral	N	0.458083311	None	None	I
E/L	0.7944	likely_pathogenic	0.8033	pathogenic	0.049	Stabilizing	0.919	D	0.521	neutral	None	None	None	None	I
E/M	0.7594	likely_pathogenic	0.766	pathogenic	0.324	Stabilizing	0.999	D	0.587	neutral	None	None	None	None	I
E/N	0.4454	ambiguous	0.4633	ambiguous	-0.681	Destabilizing	0.988	D	0.407	neutral	None	None	None	None	I
E/P	0.9843	likely_pathogenic	0.98	pathogenic	-0.176	Destabilizing	0.988	D	0.434	neutral	None	None	None	None	I
E/Q	0.2634	likely_benign	0.2728	benign	-0.605	Destabilizing	0.984	D	0.445	neutral	N	0.45570268	None	None	I
E/R	0.5995	likely_pathogenic	0.6034	pathogenic	-0.128	Destabilizing	0.988	D	0.404	neutral	None	None	None	None	I
E/S	0.4099	ambiguous	0.4243	ambiguous	-0.922	Destabilizing	0.851	D	0.386	neutral	None	None	None	None	I
E/T	0.5004	ambiguous	0.4991	ambiguous	-0.705	Destabilizing	0.919	D	0.397	neutral	None	None	None	None	I
E/V	0.5894	likely_pathogenic	0.5713	pathogenic	-0.176	Destabilizing	0.811	D	0.46	neutral	D	0.626335982	None	None	I
E/W	0.9775	likely_pathogenic	0.9787	pathogenic	-0.209	Destabilizing	0.997	D	0.679	prob.neutral	None	None	None	None	I
E/Y	0.8682	likely_pathogenic	0.8834	pathogenic	-0.176	Destabilizing	0.261	N	0.313	neutral	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.