TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33218	99877;99878;99879	chr2:178537555;178537554;178537553	chr2:179402282;179402281;179402280
N2AB	31577	94954;94955;94956	chr2:178537555;178537554;178537553	chr2:179402282;179402281;179402280
N2A	30650	92173;92174;92175	chr2:178537555;178537554;178537553	chr2:179402282;179402281;179402280
N2B	24153	72682;72683;72684	chr2:178537555;178537554;178537553	chr2:179402282;179402281;179402280
Novex-1	24278	73057;73058;73059	chr2:178537555;178537554;178537553	chr2:179402282;179402281;179402280
Novex-2	24345	73258;73259;73260	chr2:178537555;178537554;178537553	chr2:179402282;179402281;179402280
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-157
• Domain position: 16
• Structural Position: 33
• Q(SASA): 0.1346
• 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	rs1692185299	None	0.014	N	0.467	0.111	0.421184727016	gnomAD-4.0.0	2.66855E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.32807E-05	0	3.31367E-05

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	0.6491	likely_pathogenic	0.6231	pathogenic	-2.125	Highly Destabilizing	0.994	D	0.684	prob.neutral	N	0.467772262	None	None	N
V/C	0.9254	likely_pathogenic	0.9207	pathogenic	-1.265	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/D	0.9932	likely_pathogenic	0.9908	pathogenic	-2.733	Highly Destabilizing	1.0	D	0.872	deleterious	N	0.468293095	None	None	N
V/E	0.983	likely_pathogenic	0.9776	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/F	0.6194	likely_pathogenic	0.6535	pathogenic	-1.454	Destabilizing	1.0	D	0.827	deleterious	N	0.4566833	None	None	N
V/G	0.8463	likely_pathogenic	0.8133	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.847	deleterious	N	0.4566833	None	None	N
V/H	0.9931	likely_pathogenic	0.991	pathogenic	-2.176	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/I	0.1054	likely_benign	0.1181	benign	-0.835	Destabilizing	0.014	N	0.467	neutral	N	0.472775437	None	None	N
V/K	0.9853	likely_pathogenic	0.9782	pathogenic	-1.796	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/L	0.4564	ambiguous	0.4881	ambiguous	-0.835	Destabilizing	0.935	D	0.727	prob.delet.	N	0.476162459	None	None	N
V/M	0.4667	ambiguous	0.4967	ambiguous	-0.577	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/N	0.9768	likely_pathogenic	0.9692	pathogenic	-2.012	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/P	0.9949	likely_pathogenic	0.9941	pathogenic	-1.241	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/Q	0.9768	likely_pathogenic	0.9684	pathogenic	-1.962	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/R	0.9747	likely_pathogenic	0.9638	pathogenic	-1.469	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/S	0.8998	likely_pathogenic	0.8754	pathogenic	-2.544	Highly Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
V/T	0.7636	likely_pathogenic	0.7058	pathogenic	-2.232	Highly Destabilizing	0.989	D	0.759	deleterious	None	None	None	None	N
V/W	0.9946	likely_pathogenic	0.9953	pathogenic	-1.912	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Y	0.9715	likely_pathogenic	0.97	pathogenic	-1.529	Destabilizing	1.0	D	0.841	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.