TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22433	67522;67523;67524	chr2:178579990;178579989;178579988	chr2:179444717;179444716;179444715
N2AB	20792	62599;62600;62601	chr2:178579990;178579989;178579988	chr2:179444717;179444716;179444715
N2A	19865	59818;59819;59820	chr2:178579990;178579989;178579988	chr2:179444717;179444716;179444715
N2B	13368	40327;40328;40329	chr2:178579990;178579989;178579988	chr2:179444717;179444716;179444715
Novex-1	13493	40702;40703;40704	chr2:178579990;178579989;178579988	chr2:179444717;179444716;179444715
Novex-2	13560	40903;40904;40905	chr2:178579990;178579989;178579988	chr2:179444717;179444716;179444715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-50
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.4682
• 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	None	None	0.704	N	0.298	0.074	0.194818534648	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/G	rs2047336036	None	0.826	N	0.423	0.235	0.285316908763	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs2047336036	None	0.826	N	0.423	0.235	0.285316908763	gnomAD-4.0.0	6.5741E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47076E-05	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
E/A	0.2758	likely_benign	0.3482	ambiguous	-0.834	Destabilizing	0.134	N	0.173	neutral	N	0.497546169	None	None	I
E/C	0.9371	likely_pathogenic	0.9523	pathogenic	-0.449	Destabilizing	0.999	D	0.399	neutral	None	None	None	None	I
E/D	0.3701	ambiguous	0.4485	ambiguous	-0.54	Destabilizing	0.704	D	0.298	neutral	N	0.515478569	None	None	I
E/F	0.9449	likely_pathogenic	0.9688	pathogenic	-0.337	Destabilizing	0.991	D	0.435	neutral	None	None	None	None	I
E/G	0.5205	ambiguous	0.6441	pathogenic	-1.086	Destabilizing	0.826	D	0.423	neutral	N	0.471677364	None	None	I
E/H	0.8007	likely_pathogenic	0.8775	pathogenic	-0.053	Destabilizing	0.991	D	0.25	neutral	None	None	None	None	I
E/I	0.4483	ambiguous	0.497	ambiguous	-0.172	Destabilizing	0.17	N	0.397	neutral	None	None	None	None	I
E/K	0.2609	likely_benign	0.4035	ambiguous	-0.059	Destabilizing	0.92	D	0.293	neutral	N	0.453352675	None	None	I
E/L	0.684	likely_pathogenic	0.7724	pathogenic	-0.172	Destabilizing	0.759	D	0.446	neutral	None	None	None	None	I
E/M	0.676	likely_pathogenic	0.7331	pathogenic	-0.015	Destabilizing	0.991	D	0.411	neutral	None	None	None	None	I
E/N	0.5822	likely_pathogenic	0.6802	pathogenic	-0.647	Destabilizing	0.079	N	0.107	neutral	None	None	None	None	I
E/P	0.7124	likely_pathogenic	0.8235	pathogenic	-0.373	Destabilizing	0.997	D	0.378	neutral	None	None	None	None	I
E/Q	0.2446	likely_benign	0.3176	benign	-0.556	Destabilizing	0.959	D	0.282	neutral	N	0.505146932	None	None	I
E/R	0.4276	ambiguous	0.5934	pathogenic	0.327	Stabilizing	0.969	D	0.277	neutral	None	None	None	None	I
E/S	0.453	ambiguous	0.5511	ambiguous	-0.814	Destabilizing	0.759	D	0.288	neutral	None	None	None	None	I
E/T	0.3952	ambiguous	0.5	ambiguous	-0.593	Destabilizing	0.939	D	0.368	neutral	None	None	None	None	I
E/V	0.3356	likely_benign	0.4031	ambiguous	-0.373	Destabilizing	0.704	D	0.422	neutral	N	0.465772924	None	None	I
E/W	0.9879	likely_pathogenic	0.994	pathogenic	-0.017	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	I
E/Y	0.8947	likely_pathogenic	0.9406	pathogenic	-0.069	Destabilizing	0.997	D	0.432	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.