TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	963	3112;3113;3114	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744
N2AB	963	3112;3113;3114	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744
N2A	963	3112;3113;3114	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744
N2B	917	2974;2975;2976	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744
Novex-1	917	2974;2975;2976	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744
Novex-2	917	2974;2975;2976	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744
Novex-3	963	3112;3113;3114	chr2:178783019;178783018;178783017	chr2:179647746;179647745;179647744

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-3
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2523
• 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/D	rs1393032636	-1.404	0.434	N	0.251	0.237	0.219573609325	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.63988E-04
E/D	rs1393032636	-1.404	0.434	N	0.251	0.237	0.219573609325	gnomAD-4.0.0	1.59056E-06	None	None	None	None	N	None	0	2.28624E-05	None	0	0	None	0	0	0	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	0.3914	ambiguous	0.4826	ambiguous	-0.867	Destabilizing	0.998	D	0.607	neutral	D	0.555401178	None	None	N
E/C	0.9793	likely_pathogenic	0.9849	pathogenic	-0.599	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.6848	likely_pathogenic	0.7506	pathogenic	-1.391	Destabilizing	0.434	N	0.251	neutral	N	0.512002518	None	None	N
E/F	0.9703	likely_pathogenic	0.9799	pathogenic	-0.347	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/G	0.7319	likely_pathogenic	0.8071	pathogenic	-1.252	Destabilizing	0.999	D	0.705	prob.neutral	D	0.608524531	None	None	N
E/H	0.907	likely_pathogenic	0.9386	pathogenic	-0.728	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/I	0.7197	likely_pathogenic	0.777	pathogenic	0.192	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/K	0.7068	likely_pathogenic	0.7943	pathogenic	-0.985	Destabilizing	0.998	D	0.524	neutral	N	0.503373505	None	None	N
E/L	0.831	likely_pathogenic	0.8789	pathogenic	0.192	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/M	0.8152	likely_pathogenic	0.8595	pathogenic	0.665	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/N	0.8286	likely_pathogenic	0.876	pathogenic	-1.375	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
E/P	0.9965	likely_pathogenic	0.9981	pathogenic	-0.14	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/Q	0.3279	likely_benign	0.3788	ambiguous	-1.22	Destabilizing	0.999	D	0.664	neutral	N	0.511456543	None	None	N
E/R	0.8086	likely_pathogenic	0.873	pathogenic	-0.705	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/S	0.5405	ambiguous	0.6234	pathogenic	-1.728	Destabilizing	0.997	D	0.571	neutral	None	None	None	None	N
E/T	0.5427	ambiguous	0.6248	pathogenic	-1.415	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/V	0.4836	ambiguous	0.5468	ambiguous	-0.14	Destabilizing	1.0	D	0.749	deleterious	D	0.538670535	None	None	N
E/W	0.9935	likely_pathogenic	0.9958	pathogenic	-0.175	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Y	0.9621	likely_pathogenic	0.9751	pathogenic	-0.131	Destabilizing	1.0	D	0.787	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.