TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17098	51517;51518;51519	chr2:178610234;178610233;178610232	chr2:179474961;179474960;179474959
N2AB	15457	46594;46595;46596	chr2:178610234;178610233;178610232	chr2:179474961;179474960;179474959
N2A	14530	43813;43814;43815	chr2:178610234;178610233;178610232	chr2:179474961;179474960;179474959
N2B	8033	24322;24323;24324	chr2:178610234;178610233;178610232	chr2:179474961;179474960;179474959
Novex-1	8158	24697;24698;24699	chr2:178610234;178610233;178610232	chr2:179474961;179474960;179474959
Novex-2	8225	24898;24899;24900	chr2:178610234;178610233;178610232	chr2:179474961;179474960;179474959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-12
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.157
• 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
M/L	None	None	0.927	N	0.278	0.36	0.52633505579	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	5.67344E-05	0	None	0	0	None	0	0	0	0	0
M/T	None	None	0.994	N	0.551	0.497	0.735427462381	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
M/A	0.7639	likely_pathogenic	0.7394	pathogenic	-2.094	Highly Destabilizing	0.989	D	0.54	neutral	None	None	None	None	N
M/C	0.8208	likely_pathogenic	0.8145	pathogenic	-1.995	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
M/D	0.9842	likely_pathogenic	0.9811	pathogenic	-1.59	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
M/E	0.9116	likely_pathogenic	0.9043	pathogenic	-1.368	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
M/F	0.5795	likely_pathogenic	0.548	ambiguous	-0.689	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	N
M/G	0.9344	likely_pathogenic	0.9172	pathogenic	-2.579	Highly Destabilizing	0.995	D	0.646	neutral	None	None	None	None	N
M/H	0.8638	likely_pathogenic	0.8392	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
M/I	0.7625	likely_pathogenic	0.7698	pathogenic	-0.717	Destabilizing	0.985	D	0.533	neutral	N	0.44629063	None	None	N
M/K	0.6799	likely_pathogenic	0.6391	pathogenic	-1.206	Destabilizing	0.994	D	0.552	neutral	N	0.452139166	None	None	N
M/L	0.2607	likely_benign	0.2569	benign	-0.717	Destabilizing	0.927	D	0.278	neutral	N	0.415565078	None	None	N
M/N	0.8625	likely_pathogenic	0.8566	pathogenic	-1.593	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
M/P	0.9929	likely_pathogenic	0.9907	pathogenic	-1.156	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
M/Q	0.616	likely_pathogenic	0.5928	pathogenic	-1.302	Destabilizing	0.999	D	0.529	neutral	None	None	None	None	N
M/R	0.7395	likely_pathogenic	0.6986	pathogenic	-1.209	Destabilizing	0.998	D	0.589	neutral	N	0.456718267	None	None	N
M/S	0.8044	likely_pathogenic	0.7865	pathogenic	-2.204	Highly Destabilizing	0.995	D	0.52	neutral	None	None	None	None	N
M/T	0.7286	likely_pathogenic	0.7232	pathogenic	-1.844	Destabilizing	0.994	D	0.551	neutral	N	0.406153374	None	None	N
M/V	0.2914	likely_benign	0.2981	benign	-1.156	Destabilizing	0.985	D	0.457	neutral	N	0.419162743	None	None	N
M/W	0.934	likely_pathogenic	0.9247	pathogenic	-0.954	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
M/Y	0.8652	likely_pathogenic	0.8435	pathogenic	-0.913	Destabilizing	0.999	D	0.643	neutral	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.