TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23036	69331;69332;69333	chr2:178577229;178577228;178577227	chr2:179441956;179441955;179441954
N2AB	21395	64408;64409;64410	chr2:178577229;178577228;178577227	chr2:179441956;179441955;179441954
N2A	20468	61627;61628;61629	chr2:178577229;178577228;178577227	chr2:179441956;179441955;179441954
N2B	13971	42136;42137;42138	chr2:178577229;178577228;178577227	chr2:179441956;179441955;179441954
Novex-1	14096	42511;42512;42513	chr2:178577229;178577228;178577227	chr2:179441956;179441955;179441954
Novex-2	14163	42712;42713;42714	chr2:178577229;178577228;178577227	chr2:179441956;179441955;179441954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-128
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.7102
• 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
T/A	None	None	0.027	D	0.406	0.165	0.286848849266	gnomAD-4.0.0	3.18532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71997E-06	0	0
T/I	rs1056452429	0.095	0.317	N	0.443	0.216	0.40146981186	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
T/I	rs1056452429	0.095	0.317	N	0.443	0.216	0.40146981186	gnomAD-4.0.0	1.36897E-06	None	None	None	None	N	None	0	2.23774E-05	None	0	0	None	0	0	8.99649E-07	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
T/A	0.0894	likely_benign	0.0848	benign	-0.814	Destabilizing	0.027	N	0.406	neutral	D	0.536041134	None	None	N
T/C	0.3264	likely_benign	0.3204	benign	-0.531	Destabilizing	0.824	D	0.436	neutral	None	None	None	None	N
T/D	0.4105	ambiguous	0.3653	ambiguous	0.201	Stabilizing	0.081	N	0.421	neutral	None	None	None	None	N
T/E	0.313	likely_benign	0.2646	benign	0.215	Stabilizing	0.081	N	0.421	neutral	None	None	None	None	N
T/F	0.2402	likely_benign	0.2236	benign	-0.841	Destabilizing	0.555	D	0.468	neutral	None	None	None	None	N
T/G	0.2903	likely_benign	0.3228	benign	-1.078	Destabilizing	0.081	N	0.455	neutral	None	None	None	None	N
T/H	0.1893	likely_benign	0.1674	benign	-1.303	Destabilizing	0.824	D	0.449	neutral	None	None	None	None	N
T/I	0.1303	likely_benign	0.1138	benign	-0.2	Destabilizing	0.317	N	0.443	neutral	N	0.515532576	None	None	N
T/K	0.139	likely_benign	0.1205	benign	-0.565	Destabilizing	None	N	0.155	neutral	N	0.469104066	None	None	N
T/L	0.0902	likely_benign	0.0843	benign	-0.2	Destabilizing	0.149	N	0.435	neutral	None	None	None	None	N
T/M	0.0806	likely_benign	0.074	benign	-0.051	Destabilizing	0.791	D	0.424	neutral	None	None	None	None	N
T/N	0.1071	likely_benign	0.1024	benign	-0.514	Destabilizing	0.081	N	0.345	neutral	None	None	None	None	N
T/P	0.6615	likely_pathogenic	0.6648	pathogenic	-0.372	Destabilizing	0.317	N	0.425	neutral	D	0.532869659	None	None	N
T/Q	0.1837	likely_benign	0.1637	benign	-0.631	Destabilizing	0.38	N	0.425	neutral	None	None	None	None	N
T/R	0.1358	likely_benign	0.1163	benign	-0.42	Destabilizing	0.062	N	0.399	neutral	D	0.535465131	None	None	N
T/S	0.1106	likely_benign	0.1121	benign	-0.874	Destabilizing	None	N	0.156	neutral	N	0.514665784	None	None	N
T/V	0.1145	likely_benign	0.1009	benign	-0.372	Destabilizing	0.149	N	0.348	neutral	None	None	None	None	N
T/W	0.5425	ambiguous	0.5295	ambiguous	-0.752	Destabilizing	0.935	D	0.544	neutral	None	None	None	None	N
T/Y	0.2573	likely_benign	0.2429	benign	-0.514	Destabilizing	0.555	D	0.467	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.