TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7403	22432;22433;22434	chr2:178722692;178722691;178722690	chr2:179587419;179587418;179587417
N2AB	7086	21481;21482;21483	chr2:178722692;178722691;178722690	chr2:179587419;179587418;179587417
N2A	6159	18700;18701;18702	chr2:178722692;178722691;178722690	chr2:179587419;179587418;179587417
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-58
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.471
• Predicted PPI site: I

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
T/I	None	None	0.939	N	0.447	0.213	0.493021045079	gnomAD-4.0.0	1.59318E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43451E-05	0
T/N	rs2078617852	None	0.684	N	0.277	0.17	0.376745185316	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/N	rs2078617852	None	0.684	N	0.277	0.17	0.376745185316	gnomAD-4.0.0	6.57402E-06	None	None	None	None	I	None	2.41278E-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
T/A	0.0705	likely_benign	0.0766	benign	-0.542	Destabilizing	0.309	N	0.255	neutral	N	0.426814726	None	None	I
T/C	0.3472	ambiguous	0.3897	ambiguous	-0.309	Destabilizing	0.996	D	0.471	neutral	None	None	None	None	I
T/D	0.248	likely_benign	0.3112	benign	-0.072	Destabilizing	0.742	D	0.393	neutral	None	None	None	None	I
T/E	0.1597	likely_benign	0.2063	benign	-0.141	Destabilizing	0.742	D	0.412	neutral	None	None	None	None	I
T/F	0.1231	likely_benign	0.143	benign	-0.894	Destabilizing	0.953	D	0.537	neutral	None	None	None	None	I
T/G	0.2047	likely_benign	0.2466	benign	-0.702	Destabilizing	0.373	N	0.494	neutral	None	None	None	None	I
T/H	0.1694	likely_benign	0.1997	benign	-0.965	Destabilizing	0.02	N	0.403	neutral	None	None	None	None	I
T/I	0.1099	likely_benign	0.1263	benign	-0.229	Destabilizing	0.939	D	0.447	neutral	N	0.472376445	None	None	I
T/K	0.1261	likely_benign	0.1672	benign	-0.545	Destabilizing	0.742	D	0.399	neutral	None	None	None	None	I
T/L	0.0847	likely_benign	0.091	benign	-0.229	Destabilizing	0.742	D	0.41	neutral	None	None	None	None	I
T/M	0.0759	likely_benign	0.0775	benign	0.07	Stabilizing	0.984	D	0.468	neutral	None	None	None	None	I
T/N	0.0972	likely_benign	0.1046	benign	-0.284	Destabilizing	0.684	D	0.277	neutral	N	0.482014648	None	None	I
T/P	0.2223	likely_benign	0.3099	benign	-0.304	Destabilizing	0.007	N	0.236	neutral	N	0.488633976	None	None	I
T/Q	0.1513	likely_benign	0.1824	benign	-0.574	Destabilizing	0.91	D	0.449	neutral	None	None	None	None	I
T/R	0.1035	likely_benign	0.138	benign	-0.183	Destabilizing	0.91	D	0.435	neutral	None	None	None	None	I
T/S	0.0855	likely_benign	0.0907	benign	-0.526	Destabilizing	0.012	N	0.115	neutral	N	0.375404471	None	None	I
T/V	0.0985	likely_benign	0.1045	benign	-0.304	Destabilizing	0.742	D	0.277	neutral	None	None	None	None	I
T/W	0.3787	ambiguous	0.4647	ambiguous	-0.833	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	I
T/Y	0.1716	likely_benign	0.2014	benign	-0.595	Destabilizing	0.91	D	0.534	neutral	None	None	None	None	I

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.