TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20460	61603;61604;61605	chr2:178590347;178590346;178590345	chr2:179455074;179455073;179455072
N2AB	18819	56680;56681;56682	chr2:178590347;178590346;178590345	chr2:179455074;179455073;179455072
N2A	17892	53899;53900;53901	chr2:178590347;178590346;178590345	chr2:179455074;179455073;179455072
N2B	11395	34408;34409;34410	chr2:178590347;178590346;178590345	chr2:179455074;179455073;179455072
Novex-1	11520	34783;34784;34785	chr2:178590347;178590346;178590345	chr2:179455074;179455073;179455072
Novex-2	11587	34984;34985;34986	chr2:178590347;178590346;178590345	chr2:179455074;179455073;179455072
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-36
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.3582
• 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
E/Q	None	None	0.999	D	0.79	0.279	0.539612970712	gnomAD-4.0.0	1.70076E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.01951E-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
E/A	0.4126	ambiguous	0.3774	ambiguous	-0.427	Destabilizing	0.997	D	0.789	deleterious	N	0.50263785	None	None	N
E/C	0.9286	likely_pathogenic	0.9262	pathogenic	-0.356	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/D	0.2895	likely_benign	0.268	benign	-0.965	Destabilizing	0.997	D	0.758	deleterious	N	0.468178559	None	None	N
E/F	0.8558	likely_pathogenic	0.8268	pathogenic	0.446	Stabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
E/G	0.6162	likely_pathogenic	0.5537	ambiguous	-0.816	Destabilizing	0.999	D	0.728	deleterious	N	0.485096899	None	None	N
E/H	0.835	likely_pathogenic	0.794	pathogenic	0.401	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/I	0.4997	ambiguous	0.4469	ambiguous	0.637	Stabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
E/K	0.6765	likely_pathogenic	0.5713	pathogenic	-0.272	Destabilizing	0.997	D	0.811	deleterious	D	0.528898944	None	None	N
E/L	0.5616	ambiguous	0.5263	ambiguous	0.637	Stabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/M	0.6103	likely_pathogenic	0.5649	pathogenic	0.823	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
E/N	0.6617	likely_pathogenic	0.5977	pathogenic	-0.985	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
E/P	0.761	likely_pathogenic	0.7157	pathogenic	0.304	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/Q	0.3957	ambiguous	0.335	benign	-0.797	Destabilizing	0.999	D	0.79	deleterious	D	0.527688223	None	None	N
E/R	0.7904	likely_pathogenic	0.7138	pathogenic	0.131	Stabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
E/S	0.5794	likely_pathogenic	0.5218	ambiguous	-1.252	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
E/T	0.5375	ambiguous	0.4783	ambiguous	-0.914	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
E/V	0.3247	likely_benign	0.2852	benign	0.304	Stabilizing	0.999	D	0.765	deleterious	N	0.486248988	None	None	N
E/W	0.9636	likely_pathogenic	0.9524	pathogenic	0.732	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Y	0.8101	likely_pathogenic	0.7703	pathogenic	0.73	Stabilizing	1.0	D	0.863	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.