TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14510	43753;43754;43755	chr2:178632366;178632365;178632364	chr2:179497093;179497092;179497091
N2AB	12869	38830;38831;38832	chr2:178632366;178632365;178632364	chr2:179497093;179497092;179497091
N2A	11942	36049;36050;36051	chr2:178632366;178632365;178632364	chr2:179497093;179497092;179497091
N2B	5445	16558;16559;16560	chr2:178632366;178632365;178632364	chr2:179497093;179497092;179497091
Novex-1	5570	16933;16934;16935	chr2:178632366;178632365;178632364	chr2:179497093;179497092;179497091
Novex-2	5637	17134;17135;17136	chr2:178632366;178632365;178632364	chr2:179497093;179497092;179497091
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-96
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.3211
• 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	None	None	0.999	D	0.445	0.5	0.415564226483	gnomAD-4.0.0	1.61706E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89949E-06	0	0
E/Q	rs769619291	-0.996	1.0	D	0.625	0.516	0.593630346942	gnomAD-2.1.1	4.3E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.56E-06	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	0.5405	ambiguous	0.6167	pathogenic	-0.878	Destabilizing	0.999	D	0.613	neutral	D	0.627429502	None	None	N
E/C	0.9881	likely_pathogenic	0.9918	pathogenic	-0.5	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/D	0.8142	likely_pathogenic	0.8436	pathogenic	-1.1	Destabilizing	0.999	D	0.445	neutral	D	0.69218391	None	None	N
E/F	0.986	likely_pathogenic	0.9906	pathogenic	-0.385	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/G	0.5081	ambiguous	0.5763	pathogenic	-1.228	Destabilizing	1.0	D	0.673	neutral	D	0.693572591	None	None	N
E/H	0.9665	likely_pathogenic	0.9767	pathogenic	-0.663	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/I	0.8446	likely_pathogenic	0.8864	pathogenic	0.071	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/K	0.6085	likely_pathogenic	0.7243	pathogenic	-0.627	Destabilizing	0.999	D	0.591	neutral	D	0.598999775	None	None	N
E/L	0.8955	likely_pathogenic	0.922	pathogenic	0.071	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
E/M	0.8945	likely_pathogenic	0.9242	pathogenic	0.472	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/N	0.8884	likely_pathogenic	0.9087	pathogenic	-1.057	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/P	0.9367	likely_pathogenic	0.9538	pathogenic	-0.224	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/Q	0.4748	ambiguous	0.522	ambiguous	-0.945	Destabilizing	1.0	D	0.625	neutral	D	0.69218391	None	None	N
E/R	0.7564	likely_pathogenic	0.8305	pathogenic	-0.365	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/S	0.7974	likely_pathogenic	0.8427	pathogenic	-1.357	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
E/T	0.8085	likely_pathogenic	0.8567	pathogenic	-1.07	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/V	0.6591	likely_pathogenic	0.7519	pathogenic	-0.224	Destabilizing	1.0	D	0.715	prob.delet.	D	0.621736318	None	None	N
E/W	0.9945	likely_pathogenic	0.9961	pathogenic	-0.145	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/Y	0.9741	likely_pathogenic	0.9827	pathogenic	-0.139	Destabilizing	1.0	D	0.706	prob.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.