TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5512	16759;16760;16761	chr2:178732527;178732526;178732525	chr2:179597254;179597253;179597252
N2AB	5195	15808;15809;15810	chr2:178732527;178732526;178732525	chr2:179597254;179597253;179597252
N2A	4268	13027;13028;13029	chr2:178732527;178732526;178732525	chr2:179597254;179597253;179597252
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-38
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0792
• 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
V/I	None	None	0.962	N	0.497	0.364	0.645824608598	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
V/A	0.2598	likely_benign	0.267	benign	-2.069	Highly Destabilizing	0.996	D	0.507	neutral	D	0.528557801	None	None	N
V/C	0.8572	likely_pathogenic	0.8536	pathogenic	-1.935	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
V/D	0.9502	likely_pathogenic	0.9604	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/E	0.8889	likely_pathogenic	0.9074	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.709	prob.delet.	D	0.565135512	None	None	N
V/F	0.6685	likely_pathogenic	0.704	pathogenic	-1.404	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
V/G	0.4725	ambiguous	0.5011	ambiguous	-2.516	Highly Destabilizing	1.0	D	0.724	prob.delet.	D	0.547031257	None	None	N
V/H	0.9739	likely_pathogenic	0.9785	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
V/I	0.1176	likely_benign	0.1232	benign	-0.867	Destabilizing	0.962	D	0.497	neutral	N	0.494521555	None	None	N
V/K	0.9362	likely_pathogenic	0.9521	pathogenic	-1.678	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
V/L	0.346	ambiguous	0.3596	ambiguous	-0.867	Destabilizing	0.275	N	0.302	neutral	D	0.539932375	None	None	N
V/M	0.4097	ambiguous	0.4427	ambiguous	-0.991	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
V/N	0.8651	likely_pathogenic	0.8861	pathogenic	-1.798	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/P	0.7316	likely_pathogenic	0.7718	pathogenic	-1.238	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
V/Q	0.8853	likely_pathogenic	0.9008	pathogenic	-1.809	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/R	0.9045	likely_pathogenic	0.9207	pathogenic	-1.337	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
V/S	0.5694	likely_pathogenic	0.5813	pathogenic	-2.464	Highly Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
V/T	0.3783	ambiguous	0.3939	ambiguous	-2.203	Highly Destabilizing	0.997	D	0.625	neutral	None	None	None	None	N
V/W	0.9855	likely_pathogenic	0.9884	pathogenic	-1.71	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
V/Y	0.9614	likely_pathogenic	0.9663	pathogenic	-1.395	Destabilizing	1.0	D	0.725	prob.delet.	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.