TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28135	84628;84629;84630	chr2:178561729;178561728;178561727	chr2:179426456;179426455;179426454
N2AB	26494	79705;79706;79707	chr2:178561729;178561728;178561727	chr2:179426456;179426455;179426454
N2A	25567	76924;76925;76926	chr2:178561729;178561728;178561727	chr2:179426456;179426455;179426454
N2B	19070	57433;57434;57435	chr2:178561729;178561728;178561727	chr2:179426456;179426455;179426454
Novex-1	19195	57808;57809;57810	chr2:178561729;178561728;178561727	chr2:179426456;179426455;179426454
Novex-2	19262	58009;58010;58011	chr2:178561729;178561728;178561727	chr2:179426456;179426455;179426454
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-92
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.6721
• 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
Y/C	None	None	0.958	N	0.727	0.267	0.353974658523	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
Y/A	0.9467	likely_pathogenic	0.9487	pathogenic	-0.687	Destabilizing	0.272	N	0.641	neutral	None	None	None	None	I
Y/C	0.4987	ambiguous	0.5017	ambiguous	0.19	Stabilizing	0.958	D	0.727	prob.delet.	N	0.470532637	None	None	I
Y/D	0.9413	likely_pathogenic	0.9361	pathogenic	0.758	Stabilizing	0.331	N	0.649	neutral	N	0.497622887	None	None	I
Y/E	0.9805	likely_pathogenic	0.9786	pathogenic	0.738	Stabilizing	0.567	D	0.605	neutral	None	None	None	None	I
Y/F	0.0965	likely_benign	0.1063	benign	-0.363	Destabilizing	0.001	N	0.387	neutral	N	0.467532693	None	None	I
Y/G	0.9303	likely_pathogenic	0.9365	pathogenic	-0.88	Destabilizing	0.157	N	0.622	neutral	None	None	None	None	I
Y/H	0.6579	likely_pathogenic	0.6312	pathogenic	0.182	Stabilizing	0.667	D	0.511	neutral	N	0.469923526	None	None	I
Y/I	0.7801	likely_pathogenic	0.795	pathogenic	-0.199	Destabilizing	0.396	N	0.581	neutral	None	None	None	None	I
Y/K	0.9716	likely_pathogenic	0.9719	pathogenic	0.225	Stabilizing	0.567	D	0.615	neutral	None	None	None	None	I
Y/L	0.7422	likely_pathogenic	0.7558	pathogenic	-0.199	Destabilizing	0.157	N	0.607	neutral	None	None	None	None	I
Y/M	0.876	likely_pathogenic	0.8864	pathogenic	-0.059	Destabilizing	0.909	D	0.595	neutral	None	None	None	None	I
Y/N	0.7743	likely_pathogenic	0.7759	pathogenic	0.05	Stabilizing	0.002	N	0.514	neutral	N	0.486355487	None	None	I
Y/P	0.9922	likely_pathogenic	0.9919	pathogenic	-0.342	Destabilizing	0.89	D	0.697	prob.neutral	None	None	None	None	I
Y/Q	0.9549	likely_pathogenic	0.9555	pathogenic	0.077	Stabilizing	0.567	D	0.601	neutral	None	None	None	None	I
Y/R	0.9309	likely_pathogenic	0.9366	pathogenic	0.488	Stabilizing	0.567	D	0.68	prob.neutral	None	None	None	None	I
Y/S	0.8563	likely_pathogenic	0.8745	pathogenic	-0.349	Destabilizing	0.124	N	0.61	neutral	N	0.46423876	None	None	I
Y/T	0.9516	likely_pathogenic	0.9518	pathogenic	-0.276	Destabilizing	0.567	D	0.597	neutral	None	None	None	None	I
Y/V	0.7376	likely_pathogenic	0.7623	pathogenic	-0.342	Destabilizing	0.157	N	0.605	neutral	None	None	None	None	I
Y/W	0.6129	likely_pathogenic	0.5786	pathogenic	-0.482	Destabilizing	0.909	D	0.509	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.