TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5406	16441;16442;16443	chr2:178732960;178732959;178732958	chr2:179597687;179597686;179597685
N2AB	5089	15490;15491;15492	chr2:178732960;178732959;178732958	chr2:179597687;179597686;179597685
N2A	4162	12709;12710;12711	chr2:178732960;178732959;178732958	chr2:179597687;179597686;179597685
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-37
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3743
• 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
A/P	None	None	0.662	N	0.419	0.323	0.569278965934	gnomAD-4.0.0	1.59175E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8586E-06	0	0
A/T	rs750622079	-0.431	0.166	N	0.273	0.101	0.333651784274	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.6E-05	None	0	None	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
A/C	0.4096	ambiguous	0.3973	ambiguous	-0.832	Destabilizing	0.991	D	0.375	neutral	None	None	None	None	I
A/D	0.2057	likely_benign	0.1789	benign	-0.487	Destabilizing	0.209	N	0.401	neutral	None	None	None	None	I
A/E	0.2366	likely_benign	0.2122	benign	-0.553	Destabilizing	0.005	N	0.153	neutral	N	0.420272756	None	None	I
A/F	0.2407	likely_benign	0.2395	benign	-0.836	Destabilizing	0.901	D	0.455	neutral	None	None	None	None	I
A/G	0.1241	likely_benign	0.125	benign	-0.804	Destabilizing	0.001	N	0.096	neutral	N	0.443555048	None	None	I
A/H	0.3252	likely_benign	0.3131	benign	-0.832	Destabilizing	0.004	N	0.341	neutral	None	None	None	None	I
A/I	0.1953	likely_benign	0.1908	benign	-0.251	Destabilizing	0.901	D	0.431	neutral	None	None	None	None	I
A/K	0.4234	ambiguous	0.3906	ambiguous	-0.881	Destabilizing	0.209	N	0.373	neutral	None	None	None	None	I
A/L	0.1454	likely_benign	0.1438	benign	-0.251	Destabilizing	0.561	D	0.398	neutral	None	None	None	None	I
A/M	0.2023	likely_benign	0.1982	benign	-0.36	Destabilizing	0.965	D	0.409	neutral	None	None	None	None	I
A/N	0.1661	likely_benign	0.1603	benign	-0.602	Destabilizing	0.561	D	0.415	neutral	None	None	None	None	I
A/P	0.6843	likely_pathogenic	0.6667	pathogenic	-0.329	Destabilizing	0.662	D	0.419	neutral	N	0.502987353	None	None	I
A/Q	0.2834	likely_benign	0.2736	benign	-0.759	Destabilizing	0.561	D	0.367	neutral	None	None	None	None	I
A/R	0.3377	likely_benign	0.3183	benign	-0.526	Destabilizing	0.004	N	0.243	neutral	None	None	None	None	I
A/S	0.0721	likely_benign	0.0726	benign	-0.948	Destabilizing	0.005	N	0.119	neutral	N	0.366227628	None	None	I
A/T	0.0727	likely_benign	0.0702	benign	-0.907	Destabilizing	0.166	N	0.273	neutral	N	0.366342271	None	None	I
A/V	0.1114	likely_benign	0.109	benign	-0.329	Destabilizing	0.491	N	0.262	neutral	N	0.436397002	None	None	I
A/W	0.6278	likely_pathogenic	0.6145	pathogenic	-1.086	Destabilizing	0.991	D	0.492	neutral	None	None	None	None	I
A/Y	0.3485	ambiguous	0.3319	benign	-0.693	Destabilizing	0.818	D	0.461	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.