TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5747	17464;17465;17466	chr2:178731527;178731526;178731525	chr2:179596254;179596253;179596252
N2AB	5430	16513;16514;16515	chr2:178731527;178731526;178731525	chr2:179596254;179596253;179596252
N2A	4503	13732;13733;13734	chr2:178731527;178731526;178731525	chr2:179596254;179596253;179596252
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-41
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2888
• 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
A/T	None	None	0.722	N	0.611	0.159	0.195762928549	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
A/C	0.6088	likely_pathogenic	0.6078	pathogenic	-0.789	Destabilizing	0.989	D	0.642	neutral	None	None	None	None	N
A/D	0.8818	likely_pathogenic	0.8962	pathogenic	0.109	Stabilizing	0.983	D	0.777	deleterious	N	0.488639076	None	None	N
A/E	0.7653	likely_pathogenic	0.7768	pathogenic	0.12	Stabilizing	0.961	D	0.76	deleterious	None	None	None	None	N
A/F	0.62	likely_pathogenic	0.6371	pathogenic	-0.504	Destabilizing	0.923	D	0.783	deleterious	None	None	None	None	N
A/G	0.342	ambiguous	0.3672	ambiguous	-0.781	Destabilizing	0.84	D	0.609	neutral	N	0.470027842	None	None	N
A/H	0.8745	likely_pathogenic	0.884	pathogenic	-0.851	Destabilizing	0.996	D	0.748	deleterious	None	None	None	None	N
A/I	0.2451	likely_benign	0.2546	benign	0.142	Stabilizing	0.011	N	0.407	neutral	None	None	None	None	N
A/K	0.8938	likely_pathogenic	0.8973	pathogenic	-0.588	Destabilizing	0.961	D	0.761	deleterious	None	None	None	None	N
A/L	0.2747	likely_benign	0.3047	benign	0.142	Stabilizing	0.415	N	0.487	neutral	None	None	None	None	N
A/M	0.3125	likely_benign	0.3431	ambiguous	-0.151	Destabilizing	0.923	D	0.762	deleterious	None	None	None	None	N
A/N	0.7727	likely_pathogenic	0.8042	pathogenic	-0.427	Destabilizing	0.987	D	0.789	deleterious	None	None	None	None	N
A/P	0.8762	likely_pathogenic	0.8955	pathogenic	-0.025	Destabilizing	0.983	D	0.768	deleterious	N	0.488385586	None	None	N
A/Q	0.7858	likely_pathogenic	0.7995	pathogenic	-0.419	Destabilizing	0.987	D	0.77	deleterious	None	None	None	None	N
A/R	0.838	likely_pathogenic	0.8387	pathogenic	-0.516	Destabilizing	0.961	D	0.769	deleterious	None	None	None	None	N
A/S	0.201	likely_benign	0.2203	benign	-0.944	Destabilizing	0.722	D	0.618	neutral	N	0.470027842	None	None	N
A/T	0.121	likely_benign	0.1312	benign	-0.795	Destabilizing	0.722	D	0.611	neutral	N	0.455531211	None	None	N
A/V	0.1027	likely_benign	0.1066	benign	-0.025	Destabilizing	0.003	N	0.208	neutral	N	0.416628578	None	None	N
A/W	0.9434	likely_pathogenic	0.9491	pathogenic	-0.843	Destabilizing	0.996	D	0.78	deleterious	None	None	None	None	N
A/Y	0.8149	likely_pathogenic	0.8273	pathogenic	-0.374	Destabilizing	0.961	D	0.787	deleterious	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.