TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30027	90304;90305;90306	chr2:178552821;178552820;178552819	chr2:179417548;179417547;179417546
N2AB	28386	85381;85382;85383	chr2:178552821;178552820;178552819	chr2:179417548;179417547;179417546
N2A	27459	82600;82601;82602	chr2:178552821;178552820;178552819	chr2:179417548;179417547;179417546
N2B	20962	63109;63110;63111	chr2:178552821;178552820;178552819	chr2:179417548;179417547;179417546
Novex-1	21087	63484;63485;63486	chr2:178552821;178552820;178552819	chr2:179417548;179417547;179417546
Novex-2	21154	63685;63686;63687	chr2:178552821;178552820;178552819	chr2:179417548;179417547;179417546
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: Fn3-106
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.1045
• 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/S	rs1046219672	None	0.856	N	0.596	0.235	0.269111216191	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/S	rs1046219672	None	0.856	N	0.596	0.235	0.269111216191	gnomAD-4.0.0	2.56208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78586E-06	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	0.7126	likely_pathogenic	0.6996	pathogenic	-1.584	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
A/D	0.948	likely_pathogenic	0.9544	pathogenic	-1.266	Destabilizing	0.954	D	0.819	deleterious	N	0.506612562	None	None	N
A/E	0.9014	likely_pathogenic	0.9084	pathogenic	-1.269	Destabilizing	0.965	D	0.752	deleterious	None	None	None	None	N
A/F	0.8118	likely_pathogenic	0.824	pathogenic	-1.133	Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	N
A/G	0.4131	ambiguous	0.4136	ambiguous	-1.174	Destabilizing	0.856	D	0.565	neutral	N	0.491635406	None	None	N
A/H	0.9616	likely_pathogenic	0.9637	pathogenic	-1.133	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
A/I	0.4143	ambiguous	0.4008	ambiguous	-0.435	Destabilizing	0.982	D	0.821	deleterious	None	None	None	None	N
A/K	0.9749	likely_pathogenic	0.9755	pathogenic	-0.958	Destabilizing	0.965	D	0.748	deleterious	None	None	None	None	N
A/L	0.4374	ambiguous	0.4259	ambiguous	-0.435	Destabilizing	0.887	D	0.784	deleterious	None	None	None	None	N
A/M	0.5188	ambiguous	0.5047	ambiguous	-0.722	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
A/N	0.8685	likely_pathogenic	0.8681	pathogenic	-0.891	Destabilizing	0.982	D	0.815	deleterious	None	None	None	None	N
A/P	0.2608	likely_benign	0.2301	benign	-0.566	Destabilizing	0.041	N	0.452	neutral	N	0.476098364	None	None	N
A/Q	0.9128	likely_pathogenic	0.913	pathogenic	-1.066	Destabilizing	0.982	D	0.822	deleterious	None	None	None	None	N
A/R	0.9509	likely_pathogenic	0.952	pathogenic	-0.732	Destabilizing	0.982	D	0.826	deleterious	None	None	None	None	N
A/S	0.2731	likely_benign	0.278	benign	-1.33	Destabilizing	0.856	D	0.596	neutral	N	0.499268728	None	None	N
A/T	0.2651	likely_benign	0.2612	benign	-1.232	Destabilizing	0.954	D	0.762	deleterious	N	0.504586785	None	None	N
A/V	0.1944	likely_benign	0.1846	benign	-0.566	Destabilizing	0.856	D	0.618	neutral	N	0.474687952	None	None	N
A/W	0.9768	likely_pathogenic	0.9782	pathogenic	-1.356	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
A/Y	0.9166	likely_pathogenic	0.9242	pathogenic	-0.935	Destabilizing	0.998	D	0.834	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.