TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3302	10129;10130;10131	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336
N2AB	3302	10129;10130;10131	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336
N2A	3302	10129;10130;10131	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336
N2B	3256	9991;9992;9993	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336
Novex-1	3256	9991;9992;9993	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336
Novex-2	3256	9991;9992;9993	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336
Novex-3	3302	10129;10130;10131	chr2:178764611;178764610;178764609	chr2:179629338;179629337;179629336

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-23
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.4061
• 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
F/L	rs1382593583	-0.774	0.999	N	0.478	0.523	0.637577279198	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.82E-06	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
F/A	0.9507	likely_pathogenic	0.9541	pathogenic	-1.823	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
F/C	0.9236	likely_pathogenic	0.9447	pathogenic	-0.639	Destabilizing	1.0	D	0.763	deleterious	D	0.540053104	None	None	I
F/D	0.9792	likely_pathogenic	0.9808	pathogenic	-0.043	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
F/E	0.9819	likely_pathogenic	0.9839	pathogenic	-0.021	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
F/G	0.9818	likely_pathogenic	0.9837	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
F/H	0.8865	likely_pathogenic	0.9141	pathogenic	-0.466	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
F/I	0.8285	likely_pathogenic	0.8393	pathogenic	-1.024	Destabilizing	1.0	D	0.729	prob.delet.	N	0.510899591	None	None	I
F/K	0.9803	likely_pathogenic	0.9842	pathogenic	-0.6	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
F/L	0.9718	likely_pathogenic	0.978	pathogenic	-1.024	Destabilizing	0.999	D	0.478	neutral	N	0.504899869	None	None	I
F/M	0.9104	likely_pathogenic	0.9212	pathogenic	-0.63	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
F/N	0.9289	likely_pathogenic	0.9399	pathogenic	-0.44	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
F/P	0.999	likely_pathogenic	0.9991	pathogenic	-1.277	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
F/Q	0.9631	likely_pathogenic	0.9701	pathogenic	-0.591	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
F/R	0.9547	likely_pathogenic	0.9623	pathogenic	0.076	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
F/S	0.8665	likely_pathogenic	0.8889	pathogenic	-1.279	Destabilizing	1.0	D	0.767	deleterious	N	0.499360891	None	None	I
F/T	0.9547	likely_pathogenic	0.9616	pathogenic	-1.166	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
F/V	0.8139	likely_pathogenic	0.8396	pathogenic	-1.277	Destabilizing	1.0	D	0.707	prob.neutral	N	0.508560084	None	None	I
F/W	0.8541	likely_pathogenic	0.8823	pathogenic	-0.544	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
F/Y	0.3389	likely_benign	0.4408	ambiguous	-0.615	Destabilizing	0.999	D	0.475	neutral	N	0.508497722	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.