TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4955	15088;15089;15090	chr2:178735583;178735582;178735581	chr2:179600310;179600309;179600308
N2AB	4638	14137;14138;14139	chr2:178735583;178735582;178735581	chr2:179600310;179600309;179600308
N2A	3711	11356;11357;11358	chr2:178735583;178735582;178735581	chr2:179600310;179600309;179600308
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-32
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3318
• 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
S/L	None	None	0.565	D	0.605	0.459	0.579204274476	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
S/A	0.0765	likely_benign	0.082	benign	-0.781	Destabilizing	0.349	N	0.467	neutral	N	0.507287982	None	None	N
S/C	0.1203	likely_benign	0.1271	benign	-0.514	Destabilizing	0.024	N	0.445	neutral	None	None	None	None	N
S/D	0.5019	ambiguous	0.5469	ambiguous	-0.046	Destabilizing	0.775	D	0.471	neutral	None	None	None	None	N
S/E	0.5566	ambiguous	0.6058	pathogenic	-0.088	Destabilizing	0.775	D	0.476	neutral	None	None	None	None	N
S/F	0.2607	likely_benign	0.3042	benign	-1.184	Destabilizing	0.961	D	0.729	prob.delet.	None	None	None	None	N
S/G	0.0822	likely_benign	0.0913	benign	-0.966	Destabilizing	0.775	D	0.483	neutral	None	None	None	None	N
S/H	0.4557	ambiguous	0.5165	ambiguous	-1.479	Destabilizing	0.996	D	0.635	neutral	None	None	None	None	N
S/I	0.202	likely_benign	0.2231	benign	-0.401	Destabilizing	0.858	D	0.669	neutral	None	None	None	None	N
S/K	0.6714	likely_pathogenic	0.7247	pathogenic	-0.607	Destabilizing	0.775	D	0.475	neutral	None	None	None	None	N
S/L	0.1037	likely_benign	0.109	benign	-0.401	Destabilizing	0.565	D	0.605	neutral	D	0.595523523	None	None	N
S/M	0.1888	likely_benign	0.2007	benign	-0.013	Destabilizing	0.989	D	0.639	neutral	None	None	None	None	N
S/N	0.1654	likely_benign	0.1799	benign	-0.478	Destabilizing	0.775	D	0.489	neutral	None	None	None	None	N
S/P	0.6742	likely_pathogenic	0.7343	pathogenic	-0.497	Destabilizing	0.949	D	0.651	neutral	D	0.74036245	None	None	N
S/Q	0.547	ambiguous	0.5991	pathogenic	-0.721	Destabilizing	0.961	D	0.503	neutral	None	None	None	None	N
S/R	0.5642	likely_pathogenic	0.6214	pathogenic	-0.446	Destabilizing	0.923	D	0.652	neutral	None	None	None	None	N
S/T	0.0721	likely_benign	0.0701	benign	-0.587	Destabilizing	0.003	N	0.203	neutral	N	0.511905135	None	None	N
S/V	0.2048	likely_benign	0.2254	benign	-0.497	Destabilizing	0.633	D	0.63	neutral	None	None	None	None	N
S/W	0.4347	ambiguous	0.4798	ambiguous	-1.107	Destabilizing	0.996	D	0.75	deleterious	None	None	None	None	N
S/Y	0.2507	likely_benign	0.2879	benign	-0.855	Destabilizing	0.987	D	0.727	prob.delet.	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.