TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30699	92320;92321;92322	chr2:178549627;178549626;178549625	chr2:179414354;179414353;179414352
N2AB	29058	87397;87398;87399	chr2:178549627;178549626;178549625	chr2:179414354;179414353;179414352
N2A	28131	84616;84617;84618	chr2:178549627;178549626;178549625	chr2:179414354;179414353;179414352
N2B	21634	65125;65126;65127	chr2:178549627;178549626;178549625	chr2:179414354;179414353;179414352
Novex-1	21759	65500;65501;65502	chr2:178549627;178549626;178549625	chr2:179414354;179414353;179414352
Novex-2	21826	65701;65702;65703	chr2:178549627;178549626;178549625	chr2:179414354;179414353;179414352
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-111
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6912
• 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
K/E	rs1248700593	None	0.999	N	0.603	0.432	0.283371740733	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
K/E	rs1248700593	None	0.999	N	0.603	0.432	0.283371740733	gnomAD-4.0.0	6.19682E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47616E-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
K/A	0.4485	ambiguous	0.405	ambiguous	-0.19	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	I
K/C	0.7326	likely_pathogenic	0.6936	pathogenic	-0.406	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
K/D	0.687	likely_pathogenic	0.6837	pathogenic	0.057	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
K/E	0.3194	likely_benign	0.3185	benign	0.094	Stabilizing	0.999	D	0.603	neutral	N	0.513689058	None	None	I
K/F	0.8725	likely_pathogenic	0.8801	pathogenic	-0.331	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
K/G	0.6544	likely_pathogenic	0.6212	pathogenic	-0.414	Destabilizing	1.0	D	0.556	neutral	None	None	None	None	I
K/H	0.3238	likely_benign	0.3288	benign	-0.643	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	I
K/I	0.4225	ambiguous	0.4203	ambiguous	0.333	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
K/L	0.501	ambiguous	0.483	ambiguous	0.333	Stabilizing	1.0	D	0.556	neutral	None	None	None	None	I
K/M	0.3459	ambiguous	0.3542	ambiguous	0.02	Stabilizing	1.0	D	0.609	neutral	N	0.490006472	None	None	I
K/N	0.537	ambiguous	0.5469	ambiguous	-0.02	Destabilizing	1.0	D	0.682	prob.neutral	N	0.478103508	None	None	I
K/P	0.6951	likely_pathogenic	0.6526	pathogenic	0.187	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	I
K/Q	0.1695	likely_benign	0.1659	benign	-0.116	Destabilizing	1.0	D	0.679	prob.neutral	N	0.513497056	None	None	I
K/R	0.085	likely_benign	0.0856	benign	-0.139	Destabilizing	0.999	D	0.528	neutral	N	0.47012779	None	None	I
K/S	0.5143	ambiguous	0.4912	ambiguous	-0.519	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
K/T	0.2446	likely_benign	0.2398	benign	-0.315	Destabilizing	1.0	D	0.624	neutral	N	0.485901414	None	None	I
K/V	0.395	ambiguous	0.3913	ambiguous	0.187	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	I
K/W	0.86	likely_pathogenic	0.8654	pathogenic	-0.343	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
K/Y	0.7008	likely_pathogenic	0.7204	pathogenic	-0.001	Destabilizing	1.0	D	0.624	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.