TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20506	61741;61742;61743	chr2:178590209;178590208;178590207	chr2:179454936;179454935;179454934
N2AB	18865	56818;56819;56820	chr2:178590209;178590208;178590207	chr2:179454936;179454935;179454934
N2A	17938	54037;54038;54039	chr2:178590209;178590208;178590207	chr2:179454936;179454935;179454934
N2B	11441	34546;34547;34548	chr2:178590209;178590208;178590207	chr2:179454936;179454935;179454934
Novex-1	11566	34921;34922;34923	chr2:178590209;178590208;178590207	chr2:179454936;179454935;179454934
Novex-2	11633	35122;35123;35124	chr2:178590209;178590208;178590207	chr2:179454936;179454935;179454934
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-121
• Domain position: 28
• Structural Position: 44
• Q(SASA): 0.1817
• 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
P/A	rs762173583	-1.656	0.767	N	0.483	0.592	0.442054744378	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
P/A	rs762173583	-1.656	0.767	N	0.483	0.592	0.442054744378	gnomAD-4.0.0	4.83581E-06	None	None	None	None	N	None	0	0	None	0	5.56638E-05	None	0	0	2.89032E-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
P/A	0.5762	likely_pathogenic	0.7228	pathogenic	-1.621	Destabilizing	0.767	D	0.483	neutral	N	0.519914555	None	None	N
P/C	0.9268	likely_pathogenic	0.9628	pathogenic	-1.125	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/D	0.9972	likely_pathogenic	0.9988	pathogenic	-1.561	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/E	0.9932	likely_pathogenic	0.9973	pathogenic	-1.566	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/F	0.9961	likely_pathogenic	0.9988	pathogenic	-1.381	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/G	0.9632	likely_pathogenic	0.9833	pathogenic	-1.941	Destabilizing	0.997	D	0.756	deleterious	None	None	None	None	N
P/H	0.9902	likely_pathogenic	0.9966	pathogenic	-1.571	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/I	0.931	likely_pathogenic	0.9688	pathogenic	-0.837	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/K	0.9954	likely_pathogenic	0.9981	pathogenic	-1.303	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/L	0.8515	likely_pathogenic	0.9343	pathogenic	-0.837	Destabilizing	0.999	D	0.819	deleterious	D	0.543686668	None	None	N
P/M	0.9543	likely_pathogenic	0.981	pathogenic	-0.615	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
P/N	0.9942	likely_pathogenic	0.9978	pathogenic	-1.078	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Q	0.9856	likely_pathogenic	0.9948	pathogenic	-1.27	Destabilizing	1.0	D	0.851	deleterious	D	0.571126674	None	None	N
P/R	0.9886	likely_pathogenic	0.9953	pathogenic	-0.802	Destabilizing	0.999	D	0.849	deleterious	D	0.559605785	None	None	N
P/S	0.9534	likely_pathogenic	0.9816	pathogenic	-1.592	Destabilizing	0.998	D	0.777	deleterious	D	0.559098806	None	None	N
P/T	0.8665	likely_pathogenic	0.9437	pathogenic	-1.488	Destabilizing	0.999	D	0.817	deleterious	D	0.570619695	None	None	N
P/V	0.8343	likely_pathogenic	0.9106	pathogenic	-1.064	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
P/W	0.9987	likely_pathogenic	0.9996	pathogenic	-1.575	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/Y	0.9965	likely_pathogenic	0.9989	pathogenic	-1.282	Destabilizing	1.0	D	0.85	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.