TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28911	86956;86957;86958	chr2:178559401;178559400;178559399	chr2:179424128;179424127;179424126
N2AB	27270	82033;82034;82035	chr2:178559401;178559400;178559399	chr2:179424128;179424127;179424126
N2A	26343	79252;79253;79254	chr2:178559401;178559400;178559399	chr2:179424128;179424127;179424126
N2B	19846	59761;59762;59763	chr2:178559401;178559400;178559399	chr2:179424128;179424127;179424126
Novex-1	19971	60136;60137;60138	chr2:178559401;178559400;178559399	chr2:179424128;179424127;179424126
Novex-2	20038	60337;60338;60339	chr2:178559401;178559400;178559399	chr2:179424128;179424127;179424126
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: Fn3-98
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.5613
• 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/A	rs370232500	None	0.995	N	0.649	0.509	0.423480098753	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02554E-05
E/G	None	None	1.0	N	0.603	0.518	0.504541157375	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86082E-06	0	0
E/K	None	None	0.997	N	0.705	0.333	0.407082143382	gnomAD-4.0.0	2.40069E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62506E-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	0.2779	likely_benign	0.3341	benign	-0.404	Destabilizing	0.995	D	0.649	neutral	N	0.521519107	None	None	N
E/C	0.9621	likely_pathogenic	0.9715	pathogenic	-0.072	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/D	0.5158	ambiguous	0.5409	ambiguous	-0.422	Destabilizing	0.965	D	0.607	neutral	N	0.487626615	None	None	N
E/F	0.9751	likely_pathogenic	0.9827	pathogenic	-0.27	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
E/G	0.4954	ambiguous	0.5588	ambiguous	-0.615	Destabilizing	1.0	D	0.603	neutral	N	0.479486314	None	None	N
E/H	0.9036	likely_pathogenic	0.9354	pathogenic	-0.106	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/I	0.7035	likely_pathogenic	0.7642	pathogenic	0.118	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/K	0.5042	ambiguous	0.5946	pathogenic	0.25	Stabilizing	0.997	D	0.705	prob.neutral	N	0.513286413	None	None	N
E/L	0.8287	likely_pathogenic	0.8611	pathogenic	0.118	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/M	0.7931	likely_pathogenic	0.8478	pathogenic	0.221	Stabilizing	0.998	D	0.604	neutral	None	None	None	None	N
E/N	0.7269	likely_pathogenic	0.7806	pathogenic	-0.057	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
E/P	0.6444	likely_pathogenic	0.6775	pathogenic	-0.035	Destabilizing	0.992	D	0.609	neutral	None	None	None	None	N
E/Q	0.3275	likely_benign	0.411	ambiguous	-0.027	Destabilizing	0.999	D	0.674	neutral	N	0.516961436	None	None	N
E/R	0.7021	likely_pathogenic	0.771	pathogenic	0.455	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/S	0.5447	ambiguous	0.621	pathogenic	-0.229	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
E/T	0.5738	likely_pathogenic	0.6689	pathogenic	-0.06	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	N
E/V	0.4839	ambiguous	0.55	ambiguous	-0.035	Destabilizing	0.998	D	0.608	neutral	N	0.479232824	None	None	N
E/W	0.9928	likely_pathogenic	0.9951	pathogenic	-0.114	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/Y	0.9508	likely_pathogenic	0.965	pathogenic	-0.025	Destabilizing	1.0	D	0.607	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.