TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27879	83860;83861;83862	chr2:178562497;178562496;178562495	chr2:179427224;179427223;179427222
N2AB	26238	78937;78938;78939	chr2:178562497;178562496;178562495	chr2:179427224;179427223;179427222
N2A	25311	76156;76157;76158	chr2:178562497;178562496;178562495	chr2:179427224;179427223;179427222
N2B	18814	56665;56666;56667	chr2:178562497;178562496;178562495	chr2:179427224;179427223;179427222
Novex-1	18939	57040;57041;57042	chr2:178562497;178562496;178562495	chr2:179427224;179427223;179427222
Novex-2	19006	57241;57242;57243	chr2:178562497;178562496;178562495	chr2:179427224;179427223;179427222
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-91
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1656
• 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
T/I	None	None	0.984	N	0.684	0.317	0.414930877219	gnomAD-4.0.0	2.05367E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69889E-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
T/A	0.1418	likely_benign	0.1423	benign	-0.613	Destabilizing	0.64	D	0.434	neutral	N	0.506533799	None	None	N
T/C	0.5067	ambiguous	0.507	ambiguous	-0.952	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
T/D	0.6234	likely_pathogenic	0.648	pathogenic	-1.87	Destabilizing	0.919	D	0.632	neutral	None	None	None	None	N
T/E	0.5302	ambiguous	0.5815	pathogenic	-1.83	Destabilizing	0.919	D	0.626	neutral	None	None	None	None	N
T/F	0.398	ambiguous	0.4189	ambiguous	-1.012	Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
T/G	0.3355	likely_benign	0.3241	benign	-0.838	Destabilizing	0.851	D	0.575	neutral	None	None	None	None	N
T/H	0.3267	likely_benign	0.3477	ambiguous	-1.243	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
T/I	0.5229	ambiguous	0.5697	pathogenic	-0.101	Destabilizing	0.984	D	0.684	prob.neutral	N	0.490464225	None	None	N
T/K	0.4004	ambiguous	0.4499	ambiguous	-0.671	Destabilizing	0.896	D	0.629	neutral	N	0.471559822	None	None	N
T/L	0.2287	likely_benign	0.2413	benign	-0.101	Destabilizing	0.919	D	0.579	neutral	None	None	None	None	N
T/M	0.1261	likely_benign	0.1313	benign	0.149	Stabilizing	0.999	D	0.663	neutral	None	None	None	None	N
T/N	0.2264	likely_benign	0.2339	benign	-1.109	Destabilizing	0.919	D	0.538	neutral	None	None	None	None	N
T/P	0.8998	likely_pathogenic	0.925	pathogenic	-0.242	Destabilizing	0.984	D	0.682	prob.neutral	N	0.513176836	None	None	N
T/Q	0.3592	ambiguous	0.3916	ambiguous	-1.366	Destabilizing	0.988	D	0.69	prob.neutral	None	None	None	None	N
T/R	0.3206	likely_benign	0.3781	ambiguous	-0.409	Destabilizing	0.968	D	0.691	prob.neutral	D	0.525562277	None	None	N
T/S	0.0986	likely_benign	0.0915	benign	-1.108	Destabilizing	0.046	N	0.201	neutral	N	0.374712959	None	None	N
T/V	0.3658	ambiguous	0.3925	ambiguous	-0.242	Destabilizing	0.919	D	0.515	neutral	None	None	None	None	N
T/W	0.7199	likely_pathogenic	0.7474	pathogenic	-1.115	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
T/Y	0.3956	ambiguous	0.4163	ambiguous	-0.695	Destabilizing	0.996	D	0.734	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.