TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2414	7465;7466;7467	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653
N2AB	2414	7465;7466;7467	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653
N2A	2414	7465;7466;7467	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653
N2B	2368	7327;7328;7329	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653
Novex-1	2368	7327;7328;7329	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653
Novex-2	2368	7327;7328;7329	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653
Novex-3	2414	7465;7466;7467	chr2:178773928;178773927;178773926	chr2:179638655;179638654;179638653

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-13
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.131
• 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
I/L	rs754815454	-1.128	0.001	D	0.298	0.327	0.422160833541	gnomAD-2.1.1	7.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
I/L	rs754815454	-1.128	0.001	D	0.298	0.327	0.422160833541	gnomAD-4.0.0	1.36816E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79861E-06	0	0
I/V	None	None	0.002	D	0.283	0.262	0.555277862696	gnomAD-4.0.0	4.10447E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39584E-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
I/A	0.7678	likely_pathogenic	0.7478	pathogenic	-2.894	Highly Destabilizing	0.25	N	0.676	prob.neutral	None	None	None	None	N
I/C	0.9383	likely_pathogenic	0.9322	pathogenic	-2.248	Highly Destabilizing	0.992	D	0.747	deleterious	None	None	None	None	N
I/D	0.9969	likely_pathogenic	0.9967	pathogenic	-3.627	Highly Destabilizing	0.972	D	0.811	deleterious	None	None	None	None	N
I/E	0.9863	likely_pathogenic	0.9857	pathogenic	-3.416	Highly Destabilizing	0.92	D	0.801	deleterious	None	None	None	None	N
I/F	0.5065	ambiguous	0.4859	ambiguous	-1.677	Destabilizing	0.81	D	0.729	prob.delet.	D	0.655267441	None	None	N
I/G	0.9828	likely_pathogenic	0.981	pathogenic	-3.394	Highly Destabilizing	0.92	D	0.791	deleterious	None	None	None	None	N
I/H	0.9752	likely_pathogenic	0.9735	pathogenic	-2.916	Highly Destabilizing	0.992	D	0.797	deleterious	None	None	None	None	N
I/K	0.9666	likely_pathogenic	0.9633	pathogenic	-2.478	Highly Destabilizing	0.92	D	0.793	deleterious	None	None	None	None	N
I/L	0.1974	likely_benign	0.1932	benign	-1.425	Destabilizing	0.001	N	0.298	neutral	D	0.547150037	None	None	N
I/M	0.1964	likely_benign	0.1906	benign	-1.377	Destabilizing	0.81	D	0.695	prob.neutral	D	0.693877966	None	None	N
I/N	0.9619	likely_pathogenic	0.961	pathogenic	-2.826	Highly Destabilizing	0.963	D	0.812	deleterious	D	0.72894482	None	None	N
I/P	0.9957	likely_pathogenic	0.9954	pathogenic	-1.901	Destabilizing	0.972	D	0.812	deleterious	None	None	None	None	N
I/Q	0.9641	likely_pathogenic	0.9619	pathogenic	-2.688	Highly Destabilizing	0.972	D	0.808	deleterious	None	None	None	None	N
I/R	0.9452	likely_pathogenic	0.9395	pathogenic	-2.074	Highly Destabilizing	0.92	D	0.812	deleterious	None	None	None	None	N
I/S	0.9033	likely_pathogenic	0.8993	pathogenic	-3.396	Highly Destabilizing	0.81	D	0.781	deleterious	D	0.72894482	None	None	N
I/T	0.6554	likely_pathogenic	0.6401	pathogenic	-3.068	Highly Destabilizing	0.549	D	0.695	prob.neutral	D	0.72912795	None	None	N
I/V	0.1081	likely_benign	0.1066	benign	-1.901	Destabilizing	0.002	N	0.283	neutral	D	0.579449295	None	None	N
I/W	0.9714	likely_pathogenic	0.9691	pathogenic	-2.197	Highly Destabilizing	0.992	D	0.791	deleterious	None	None	None	None	N
I/Y	0.9363	likely_pathogenic	0.933	pathogenic	-2.01	Highly Destabilizing	0.92	D	0.766	deleterious	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.