TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24703	74332;74333;74334	chr2:178572025;178572024;178572023	chr2:179436752;179436751;179436750
N2AB	23062	69409;69410;69411	chr2:178572025;178572024;178572023	chr2:179436752;179436751;179436750
N2A	22135	66628;66629;66630	chr2:178572025;178572024;178572023	chr2:179436752;179436751;179436750
N2B	15638	47137;47138;47139	chr2:178572025;178572024;178572023	chr2:179436752;179436751;179436750
Novex-1	15763	47512;47513;47514	chr2:178572025;178572024;178572023	chr2:179436752;179436751;179436750
Novex-2	15830	47713;47714;47715	chr2:178572025;178572024;178572023	chr2:179436752;179436751;179436750
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-67
• Domain position: 88
• Structural Position: 123
• Q(SASA): 0.1177
• 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
L/P	None	None	1.0	N	0.855	0.434	0.660644780661	gnomAD-4.0.0	1.36885E-06	None	None	None	None	N	None	0	0	None	0	2.5296E-05	None	0	0	8.99607E-07	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
L/A	0.7529	likely_pathogenic	0.7523	pathogenic	-1.995	Destabilizing	0.995	D	0.726	deleterious	None	None	None	None	N
L/C	0.869	likely_pathogenic	0.8742	pathogenic	-1.442	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/D	0.9892	likely_pathogenic	0.989	pathogenic	-1.52	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
L/E	0.9608	likely_pathogenic	0.96	pathogenic	-1.35	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
L/F	0.6342	likely_pathogenic	0.6136	pathogenic	-1.035	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
L/G	0.9251	likely_pathogenic	0.9214	pathogenic	-2.492	Highly Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
L/H	0.9309	likely_pathogenic	0.9271	pathogenic	-1.788	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/I	0.211	likely_benign	0.1964	benign	-0.613	Destabilizing	0.92	D	0.67	prob.neutral	None	None	None	None	N
L/K	0.9527	likely_pathogenic	0.9471	pathogenic	-1.479	Destabilizing	0.909	D	0.806	deleterious	None	None	None	None	N
L/M	0.2751	likely_benign	0.2659	benign	-0.669	Destabilizing	0.997	D	0.771	deleterious	N	0.464363664	None	None	N
L/N	0.9317	likely_pathogenic	0.9283	pathogenic	-1.623	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
L/P	0.87	likely_pathogenic	0.8785	pathogenic	-1.047	Destabilizing	1.0	D	0.855	deleterious	N	0.467700478	None	None	N
L/Q	0.8666	likely_pathogenic	0.8582	pathogenic	-1.534	Destabilizing	0.995	D	0.828	deleterious	N	0.482303335	None	None	N
L/R	0.9278	likely_pathogenic	0.9234	pathogenic	-1.195	Destabilizing	0.296	N	0.572	neutral	N	0.485835281	None	None	N
L/S	0.8959	likely_pathogenic	0.8926	pathogenic	-2.392	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
L/T	0.6678	likely_pathogenic	0.6658	pathogenic	-2.073	Highly Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
L/V	0.2403	likely_benign	0.2318	benign	-1.047	Destabilizing	0.92	D	0.651	prob.neutral	N	0.470279423	None	None	N
L/W	0.8975	likely_pathogenic	0.896	pathogenic	-1.274	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/Y	0.9251	likely_pathogenic	0.9186	pathogenic	-0.987	Destabilizing	0.995	D	0.834	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.