TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15969	48130;48131;48132	chr2:178616984;178616983;178616982	chr2:179481711;179481710;179481709
N2AB	14328	43207;43208;43209	chr2:178616984;178616983;178616982	chr2:179481711;179481710;179481709
N2A	13401	40426;40427;40428	chr2:178616984;178616983;178616982	chr2:179481711;179481710;179481709
N2B	6904	20935;20936;20937	chr2:178616984;178616983;178616982	chr2:179481711;179481710;179481709
Novex-1	7029	21310;21311;21312	chr2:178616984;178616983;178616982	chr2:179481711;179481710;179481709
Novex-2	7096	21511;21512;21513	chr2:178616984;178616983;178616982	chr2:179481711;179481710;179481709
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-109
• Domain position: 2
• Structural Position: 4
• Q(SASA): 0.6112
• 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/I	rs2057450267	None	1.0	D	0.771	0.459	0.582733548269	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs2057450267	None	1.0	D	0.771	0.459	0.582733548269	gnomAD-4.0.0	6.58345E-06	None	None	None	None	N	None	2.41464E-05	0	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	0.547	ambiguous	0.5191	ambiguous	-0.167	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
K/C	0.8553	likely_pathogenic	0.8365	pathogenic	-0.644	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/D	0.799	likely_pathogenic	0.7747	pathogenic	-0.531	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/E	0.2735	likely_benign	0.2623	benign	-0.562	Destabilizing	0.996	D	0.557	neutral	N	0.499860254	None	None	N
K/F	0.9457	likely_pathogenic	0.9378	pathogenic	-0.578	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/G	0.6573	likely_pathogenic	0.6116	pathogenic	-0.235	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/H	0.4975	ambiguous	0.4651	ambiguous	-0.277	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/I	0.628	likely_pathogenic	0.6166	pathogenic	-0.064	Destabilizing	1.0	D	0.771	deleterious	D	0.572110326	None	None	N
K/L	0.6286	likely_pathogenic	0.6139	pathogenic	-0.064	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/M	0.507	ambiguous	0.4919	ambiguous	-0.344	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/N	0.7083	likely_pathogenic	0.6772	pathogenic	-0.204	Destabilizing	0.999	D	0.688	prob.neutral	D	0.568104049	None	None	N
K/P	0.8138	likely_pathogenic	0.7859	pathogenic	-0.081	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/Q	0.1976	likely_benign	0.184	benign	-0.348	Destabilizing	0.999	D	0.676	prob.neutral	D	0.525909403	None	None	N
K/R	0.0937	likely_benign	0.0911	benign	-0.319	Destabilizing	0.64	D	0.271	neutral	N	0.499294428	None	None	N
K/S	0.6177	likely_pathogenic	0.5864	pathogenic	-0.526	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
K/T	0.3295	likely_benign	0.3151	benign	-0.471	Destabilizing	0.999	D	0.688	prob.neutral	D	0.569223317	None	None	N
K/V	0.5725	likely_pathogenic	0.5613	ambiguous	-0.081	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/W	0.9044	likely_pathogenic	0.8841	pathogenic	-0.694	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Y	0.8756	likely_pathogenic	0.8587	pathogenic	-0.379	Destabilizing	1.0	D	0.76	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.