TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9750	29473;29474;29475	chr2:178706626;178706625;178706624	chr2:179571353;179571352;179571351
N2AB	9433	28522;28523;28524	chr2:178706626;178706625;178706624	chr2:179571353;179571352;179571351
N2A	8506	25741;25742;25743	chr2:178706626;178706625;178706624	chr2:179571353;179571352;179571351
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-83
• Domain position: 53
• Structural Position: 130
• Q(SASA): 0.5315
• 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
K/N	None	None	0.993	None	0.616	0.273	0.261217442401	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.6597	likely_pathogenic	0.4984	ambiguous	0.078	Stabilizing	0.983	D	0.523	neutral	None	None	None	None	N
K/C	0.911	likely_pathogenic	0.8586	pathogenic	-0.023	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/D	0.7756	likely_pathogenic	0.658	pathogenic	-0.036	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
K/E	0.3405	ambiguous	0.2524	benign	-0.031	Destabilizing	0.977	D	0.491	neutral	None	None	None	None	N
K/F	0.9289	likely_pathogenic	0.8677	pathogenic	-0.116	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/G	0.8112	likely_pathogenic	0.6605	pathogenic	-0.124	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	N
K/H	0.4601	ambiguous	0.3871	ambiguous	-0.422	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
K/I	0.5358	ambiguous	0.4528	ambiguous	0.534	Stabilizing	0.997	D	0.689	prob.neutral	None	None	None	None	N
K/L	0.6608	likely_pathogenic	0.5299	ambiguous	0.534	Stabilizing	0.995	D	0.537	neutral	None	None	None	None	N
K/M	0.4751	ambiguous	0.3503	ambiguous	0.294	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	N
K/N	0.6044	likely_pathogenic	0.4804	ambiguous	0.365	Stabilizing	0.993	D	0.616	neutral	None	None	None	None	N
K/P	0.9802	likely_pathogenic	0.9282	pathogenic	0.41	Stabilizing	0.999	D	0.621	neutral	None	None	None	None	N
K/Q	0.2097	likely_benign	0.1685	benign	0.194	Stabilizing	0.993	D	0.613	neutral	None	None	None	None	N
K/R	0.0996	likely_benign	0.0902	benign	0.028	Stabilizing	0.235	N	0.277	neutral	None	None	None	None	N
K/S	0.6719	likely_pathogenic	0.538	ambiguous	-0.061	Destabilizing	0.983	D	0.529	neutral	None	None	None	None	N
K/T	0.3826	ambiguous	0.2773	benign	0.087	Stabilizing	0.997	D	0.602	neutral	None	None	None	None	N
K/V	0.5135	ambiguous	0.4376	ambiguous	0.41	Stabilizing	0.998	D	0.63	neutral	None	None	None	None	N
K/W	0.9167	likely_pathogenic	0.838	pathogenic	-0.159	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/Y	0.8409	likely_pathogenic	0.7527	pathogenic	0.191	Stabilizing	0.999	D	0.644	neutral	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.