TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7419	22480;22481;22482	chr2:178722532;178722531;178722530	chr2:179587259;179587258;179587257
N2AB	7102	21529;21530;21531	chr2:178722532;178722531;178722530	chr2:179587259;179587258;179587257
N2A	6175	18748;18749;18750	chr2:178722532;178722531;178722530	chr2:179587259;179587258;179587257
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-59
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1616
• 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/L	None	None	0.998	D	0.873	0.73	0.945451758466	gnomAD-4.0.0	1.59608E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86752E-06	0	0
P/S	rs1486377872	-1.619	0.992	D	0.842	0.801	0.775873742492	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
P/S	rs1486377872	-1.619	0.992	D	0.842	0.801	0.775873742492	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1486377872	-1.619	0.992	D	0.842	0.801	0.775873742492	gnomAD-4.0.0	6.20417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.48427E-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	0.7429	likely_pathogenic	0.6827	pathogenic	-1.118	Destabilizing	0.915	D	0.805	deleterious	D	0.643386674	None	None	N
P/C	0.9883	likely_pathogenic	0.9849	pathogenic	-0.935	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/D	0.9992	likely_pathogenic	0.9991	pathogenic	-0.395	Destabilizing	0.96	D	0.904	deleterious	None	None	None	None	N
P/E	0.9968	likely_pathogenic	0.9966	pathogenic	-0.439	Destabilizing	0.975	D	0.902	deleterious	None	None	None	None	N
P/F	0.9971	likely_pathogenic	0.9966	pathogenic	-1.085	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/G	0.9873	likely_pathogenic	0.9854	pathogenic	-1.367	Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
P/H	0.9951	likely_pathogenic	0.9942	pathogenic	-0.926	Destabilizing	1.0	D	0.88	deleterious	D	0.681743843	None	None	N
P/I	0.9442	likely_pathogenic	0.9391	pathogenic	-0.563	Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
P/K	0.9978	likely_pathogenic	0.9977	pathogenic	-0.668	Destabilizing	0.999	D	0.902	deleterious	None	None	None	None	N
P/L	0.8761	likely_pathogenic	0.8613	pathogenic	-0.563	Destabilizing	0.998	D	0.873	deleterious	D	0.656034288	None	None	N
P/M	0.9875	likely_pathogenic	0.9861	pathogenic	-0.476	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/N	0.9983	likely_pathogenic	0.9979	pathogenic	-0.388	Destabilizing	0.993	D	0.889	deleterious	None	None	None	None	N
P/Q	0.9927	likely_pathogenic	0.9914	pathogenic	-0.598	Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
P/R	0.9901	likely_pathogenic	0.9895	pathogenic	-0.255	Destabilizing	0.999	D	0.895	deleterious	D	0.681743843	None	None	N
P/S	0.9692	likely_pathogenic	0.9598	pathogenic	-0.98	Destabilizing	0.992	D	0.842	deleterious	D	0.656236092	None	None	N
P/T	0.954	likely_pathogenic	0.9416	pathogenic	-0.91	Destabilizing	0.192	N	0.697	prob.neutral	D	0.681542039	None	None	N
P/V	0.8684	likely_pathogenic	0.8438	pathogenic	-0.713	Destabilizing	0.991	D	0.864	deleterious	None	None	None	None	N
P/W	0.9995	likely_pathogenic	0.9994	pathogenic	-1.156	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/Y	0.9985	likely_pathogenic	0.9981	pathogenic	-0.841	Destabilizing	1.0	D	0.897	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.