TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27703	83332;83333;83334	chr2:178563025;178563024;178563023	chr2:179427752;179427751;179427750
N2AB	26062	78409;78410;78411	chr2:178563025;178563024;178563023	chr2:179427752;179427751;179427750
N2A	25135	75628;75629;75630	chr2:178563025;178563024;178563023	chr2:179427752;179427751;179427750
N2B	18638	56137;56138;56139	chr2:178563025;178563024;178563023	chr2:179427752;179427751;179427750
Novex-1	18763	56512;56513;56514	chr2:178563025;178563024;178563023	chr2:179427752;179427751;179427750
Novex-2	18830	56713;56714;56715	chr2:178563025;178563024;178563023	chr2:179427752;179427751;179427750
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-141
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.3353
• 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/Q	None	None	1.0	D	0.791	0.704	0.777365078794	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85884E-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	0.9268	likely_pathogenic	0.9366	pathogenic	-0.549	Destabilizing	1.0	D	0.738	prob.delet.	D	0.567051751	None	None	N
P/C	0.9935	likely_pathogenic	0.9947	pathogenic	-0.468	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/D	0.9895	likely_pathogenic	0.991	pathogenic	-0.527	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
P/E	0.9846	likely_pathogenic	0.9857	pathogenic	-0.661	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/F	0.9966	likely_pathogenic	0.9974	pathogenic	-0.899	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/G	0.9793	likely_pathogenic	0.9815	pathogenic	-0.671	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
P/H	0.9849	likely_pathogenic	0.9886	pathogenic	-0.336	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/I	0.9769	likely_pathogenic	0.9789	pathogenic	-0.383	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/K	0.9861	likely_pathogenic	0.9877	pathogenic	-0.457	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/L	0.9208	likely_pathogenic	0.9316	pathogenic	-0.383	Destabilizing	1.0	D	0.77	deleterious	D	0.628726451	None	None	N
P/M	0.979	likely_pathogenic	0.9808	pathogenic	-0.261	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/N	0.9879	likely_pathogenic	0.9887	pathogenic	-0.089	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/Q	0.9785	likely_pathogenic	0.9836	pathogenic	-0.399	Destabilizing	1.0	D	0.791	deleterious	D	0.578408056	None	None	N
P/R	0.9712	likely_pathogenic	0.9763	pathogenic	0.109	Stabilizing	1.0	D	0.802	deleterious	D	0.644342203	None	None	N
P/S	0.9779	likely_pathogenic	0.9807	pathogenic	-0.401	Destabilizing	1.0	D	0.765	deleterious	D	0.577901077	None	None	N
P/T	0.9363	likely_pathogenic	0.9459	pathogenic	-0.444	Destabilizing	1.0	D	0.763	deleterious	D	0.644342203	None	None	N
P/V	0.9579	likely_pathogenic	0.9606	pathogenic	-0.404	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/W	0.9974	likely_pathogenic	0.998	pathogenic	-0.967	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/Y	0.9951	likely_pathogenic	0.996	pathogenic	-0.666	Destabilizing	1.0	D	0.829	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.