TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1131	3616;3617;3618	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978
N2AB	1131	3616;3617;3618	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978
N2A	1131	3616;3617;3618	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978
N2B	1085	3478;3479;3480	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978
Novex-1	1085	3478;3479;3480	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978
Novex-2	1085	3478;3479;3480	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978
Novex-3	1131	3616;3617;3618	chr2:178781253;178781252;178781251	chr2:179645980;179645979;179645978

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-4
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3452
• 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/N	None	None	0.351	N	0.277	0.154	0.191931220699	gnomAD-4.0.0	1.59101E-06	None	None	None	None	N	None	0	0	None	4.76781E-05	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
S/A	0.0964	likely_benign	0.094	benign	-0.481	Destabilizing	0.004	N	0.106	neutral	None	None	None	None	N
S/C	0.196	likely_benign	0.1711	benign	-0.29	Destabilizing	0.921	D	0.396	neutral	D	0.648834498	None	None	N
S/D	0.5999	likely_pathogenic	0.6049	pathogenic	-0.161	Destabilizing	0.418	N	0.247	neutral	None	None	None	None	N
S/E	0.6543	likely_pathogenic	0.6532	pathogenic	-0.166	Destabilizing	0.418	N	0.283	neutral	None	None	None	None	N
S/F	0.2084	likely_benign	0.2137	benign	-0.609	Destabilizing	0.716	D	0.493	neutral	None	None	None	None	N
S/G	0.1888	likely_benign	0.1884	benign	-0.733	Destabilizing	0.183	N	0.275	neutral	N	0.510062823	None	None	N
S/H	0.4276	ambiguous	0.4333	ambiguous	-1.194	Destabilizing	0.005	N	0.255	neutral	None	None	None	None	N
S/I	0.1664	likely_benign	0.1748	benign	0.079	Stabilizing	0.002	N	0.335	neutral	N	0.510943594	None	None	N
S/K	0.8757	likely_pathogenic	0.8791	pathogenic	-0.76	Destabilizing	0.418	N	0.265	neutral	None	None	None	None	N
S/L	0.1189	likely_benign	0.1218	benign	0.079	Stabilizing	0.001	N	0.287	neutral	None	None	None	None	N
S/M	0.2053	likely_benign	0.2124	benign	0.193	Stabilizing	0.716	D	0.423	neutral	None	None	None	None	N
S/N	0.2236	likely_benign	0.2365	benign	-0.606	Destabilizing	0.351	N	0.277	neutral	N	0.511494936	None	None	N
S/P	0.9653	likely_pathogenic	0.9663	pathogenic	-0.073	Destabilizing	0.836	D	0.445	neutral	None	None	None	None	N
S/Q	0.6073	likely_pathogenic	0.6155	pathogenic	-0.683	Destabilizing	0.836	D	0.367	neutral	None	None	None	None	N
S/R	0.8036	likely_pathogenic	0.8086	pathogenic	-0.669	Destabilizing	0.523	D	0.446	neutral	N	0.506290888	None	None	N
S/T	0.0884	likely_benign	0.0876	benign	-0.58	Destabilizing	0.007	N	0.136	neutral	N	0.491666901	None	None	N
S/V	0.1997	likely_benign	0.2008	benign	-0.073	Destabilizing	0.049	N	0.373	neutral	None	None	None	None	N
S/W	0.4404	ambiguous	0.4247	ambiguous	-0.678	Destabilizing	0.983	D	0.501	neutral	None	None	None	None	N
S/Y	0.2426	likely_benign	0.2455	benign	-0.407	Destabilizing	0.716	D	0.49	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.