TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20835	62728;62729;62730	chr2:178589222;178589221;178589220	chr2:179453949;179453948;179453947
N2AB	19194	57805;57806;57807	chr2:178589222;178589221;178589220	chr2:179453949;179453948;179453947
N2A	18267	55024;55025;55026	chr2:178589222;178589221;178589220	chr2:179453949;179453948;179453947
N2B	11770	35533;35534;35535	chr2:178589222;178589221;178589220	chr2:179453949;179453948;179453947
Novex-1	11895	35908;35909;35910	chr2:178589222;178589221;178589220	chr2:179453949;179453948;179453947
Novex-2	11962	36109;36110;36111	chr2:178589222;178589221;178589220	chr2:179453949;179453948;179453947
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-122
• Domain position: 67
• Structural Position: 145
• Q(SASA): 0.7189
• 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/E	rs765319119	0.487	0.002	N	0.181	0.152	0.350746614512	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
K/E	rs765319119	0.487	0.002	N	0.181	0.152	0.350746614512	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	2.28739E-05	None	0	0	None	0	0	0	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	0.4102	ambiguous	0.4583	ambiguous	-0.036	Destabilizing	0.067	N	0.408	neutral	None	None	None	None	N
K/C	0.6223	likely_pathogenic	0.6857	pathogenic	-0.137	Destabilizing	0.935	D	0.555	neutral	None	None	None	None	N
K/D	0.7712	likely_pathogenic	0.8195	pathogenic	0.198	Stabilizing	0.081	N	0.399	neutral	None	None	None	None	N
K/E	0.3122	likely_benign	0.3601	ambiguous	0.21	Stabilizing	0.002	N	0.181	neutral	N	0.480878498	None	None	N
K/F	0.8193	likely_pathogenic	0.8513	pathogenic	-0.207	Destabilizing	0.555	D	0.491	neutral	None	None	None	None	N
K/G	0.5267	ambiguous	0.548	ambiguous	-0.259	Destabilizing	0.149	N	0.43	neutral	None	None	None	None	N
K/H	0.3753	ambiguous	0.4262	ambiguous	-0.589	Destabilizing	0.555	D	0.457	neutral	None	None	None	None	N
K/I	0.3971	ambiguous	0.4612	ambiguous	0.476	Stabilizing	0.555	D	0.487	neutral	None	None	None	None	N
K/L	0.4061	ambiguous	0.4566	ambiguous	0.476	Stabilizing	0.149	N	0.435	neutral	None	None	None	None	N
K/M	0.2903	likely_benign	0.3457	ambiguous	0.372	Stabilizing	0.915	D	0.447	neutral	N	0.488507621	None	None	N
K/N	0.6064	likely_pathogenic	0.6757	pathogenic	0.29	Stabilizing	0.117	N	0.419	neutral	N	0.510086684	None	None	N
K/P	0.9545	likely_pathogenic	0.9486	pathogenic	0.334	Stabilizing	0.555	D	0.436	neutral	None	None	None	None	N
K/Q	0.1518	likely_benign	0.1726	benign	0.085	Stabilizing	0.117	N	0.451	neutral	N	0.461274017	None	None	N
K/R	0.0828	likely_benign	0.0826	benign	-0.01	Destabilizing	None	N	0.143	neutral	N	0.483766874	None	None	N
K/S	0.5197	ambiguous	0.5837	pathogenic	-0.269	Destabilizing	0.149	N	0.386	neutral	None	None	None	None	N
K/T	0.2169	likely_benign	0.268	benign	-0.1	Destabilizing	0.117	N	0.415	neutral	N	0.439706666	None	None	N
K/V	0.3113	likely_benign	0.3608	ambiguous	0.334	Stabilizing	0.38	N	0.423	neutral	None	None	None	None	N
K/W	0.8296	likely_pathogenic	0.8459	pathogenic	-0.177	Destabilizing	0.935	D	0.621	neutral	None	None	None	None	N
K/Y	0.7336	likely_pathogenic	0.7765	pathogenic	0.179	Stabilizing	0.555	D	0.487	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.