TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4689	14290;14291;14292	chr2:178739168;178739167;178739166	chr2:179603895;179603894;179603893
N2AB	4372	13339;13340;13341	chr2:178739168;178739167;178739166	chr2:179603895;179603894;179603893
N2A	None	None	chr2:None	chr2:None
N2B	4326	13201;13202;13203	chr2:178739168;178739167;178739166	chr2:179603895;179603894;179603893
Novex-1	4451	13576;13577;13578	chr2:178739168;178739167;178739166	chr2:179603895;179603894;179603893
Novex-2	4518	13777;13778;13779	chr2:178739168;178739167;178739166	chr2:179603895;179603894;179603893
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-29
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.3859
• 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
S/L	rs772266620	0.169	0.811	D	0.716	0.533	None	gnomAD-2.1.1	1.13E-05	None	None	None	None	I	None	0	0	None	0	1.30412E-04	None	0	None	0	0	0
S/L	rs772266620	0.169	0.811	D	0.716	0.533	None	gnomAD-4.0.0	5.66341E-06	None	None	None	None	I	None	0	0	None	0	8.56018E-05	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
S/A	0.0714	likely_benign	0.0751	benign	-0.496	Destabilizing	0.026	N	0.347	neutral	D	0.597583124	None	None	I
S/C	0.134	likely_benign	0.1338	benign	-0.349	Destabilizing	0.997	D	0.712	prob.delet.	None	None	None	None	I
S/D	0.4255	ambiguous	0.5172	ambiguous	-0.214	Destabilizing	0.919	D	0.556	neutral	None	None	None	None	I
S/E	0.4225	ambiguous	0.5016	ambiguous	-0.286	Destabilizing	0.919	D	0.564	neutral	None	None	None	None	I
S/F	0.1587	likely_benign	0.17	benign	-0.923	Destabilizing	0.988	D	0.8	deleterious	None	None	None	None	I
S/G	0.1198	likely_benign	0.1346	benign	-0.656	Destabilizing	0.851	D	0.579	neutral	None	None	None	None	I
S/H	0.2671	likely_benign	0.2938	benign	-1.216	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
S/I	0.2049	likely_benign	0.2232	benign	-0.192	Destabilizing	0.976	D	0.781	deleterious	None	None	None	None	I
S/K	0.4133	ambiguous	0.4594	ambiguous	-0.658	Destabilizing	0.919	D	0.561	neutral	None	None	None	None	I
S/L	0.1037	likely_benign	0.1078	benign	-0.192	Destabilizing	0.811	D	0.716	prob.delet.	D	0.648063118	None	None	I
S/M	0.2218	likely_benign	0.2341	benign	0.164	Stabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
S/N	0.1908	likely_benign	0.2163	benign	-0.417	Destabilizing	0.919	D	0.583	neutral	None	None	None	None	I
S/P	0.5493	ambiguous	0.5916	pathogenic	-0.263	Destabilizing	0.984	D	0.739	prob.delet.	D	0.63625711	None	None	I
S/Q	0.4045	ambiguous	0.4511	ambiguous	-0.712	Destabilizing	0.988	D	0.6	neutral	None	None	None	None	I
S/R	0.3355	likely_benign	0.3742	ambiguous	-0.426	Destabilizing	0.976	D	0.749	deleterious	None	None	None	None	I
S/T	0.0787	likely_benign	0.0808	benign	-0.496	Destabilizing	0.011	N	0.299	neutral	N	0.502467075	None	None	I
S/V	0.1782	likely_benign	0.1881	benign	-0.263	Destabilizing	0.851	D	0.735	prob.delet.	None	None	None	None	I
S/W	0.3157	likely_benign	0.3377	benign	-0.889	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
S/Y	0.1476	likely_benign	0.1551	benign	-0.634	Destabilizing	0.996	D	0.804	deleterious	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.