TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6788	20587;20588;20589	chr2:178725960;178725959;178725958	chr2:179590687;179590686;179590685
N2AB	6471	19636;19637;19638	chr2:178725960;178725959;178725958	chr2:179590687;179590686;179590685
N2A	5544	16855;16856;16857	chr2:178725960;178725959;178725958	chr2:179590687;179590686;179590685
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-52
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.2713
• 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
P/L	None	None	0.919	D	0.62	0.59	0.863795767011	gnomAD-4.0.0	6.84992E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00182E-07	0	0
P/T	rs2154304599	None	0.414	D	0.463	0.553	0.604527667468	gnomAD-4.0.0	3.42457E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.50061E-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
P/A	0.2111	likely_benign	0.1492	benign	-0.996	Destabilizing	0.001	N	0.251	neutral	D	0.563998926	None	None	I
P/C	0.9122	likely_pathogenic	0.8922	pathogenic	-0.7	Destabilizing	0.99	D	0.651	neutral	None	None	None	None	I
P/D	0.9407	likely_pathogenic	0.9169	pathogenic	-0.709	Destabilizing	0.511	D	0.505	neutral	None	None	None	None	I
P/E	0.7877	likely_pathogenic	0.6876	pathogenic	-0.713	Destabilizing	0.321	N	0.491	neutral	None	None	None	None	I
P/F	0.9002	likely_pathogenic	0.8467	pathogenic	-0.779	Destabilizing	0.997	D	0.668	neutral	None	None	None	None	I
P/G	0.6921	likely_pathogenic	0.7362	pathogenic	-1.252	Destabilizing	0.604	D	0.483	neutral	None	None	None	None	I
P/H	0.7175	likely_pathogenic	0.6125	pathogenic	-0.607	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	I
P/I	0.7861	likely_pathogenic	0.6627	pathogenic	-0.406	Destabilizing	0.981	D	0.661	neutral	None	None	None	None	I
P/K	0.8654	likely_pathogenic	0.7664	pathogenic	-0.772	Destabilizing	0.938	D	0.487	neutral	None	None	None	None	I
P/L	0.4439	ambiguous	0.3194	benign	-0.406	Destabilizing	0.919	D	0.62	neutral	D	0.6175986	None	None	I
P/M	0.7621	likely_pathogenic	0.6555	pathogenic	-0.537	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	I
P/N	0.8806	likely_pathogenic	0.8332	pathogenic	-0.639	Destabilizing	0.868	D	0.593	neutral	None	None	None	None	I
P/Q	0.623	likely_pathogenic	0.4549	ambiguous	-0.766	Destabilizing	0.968	D	0.511	neutral	D	0.601982848	None	None	I
P/R	0.7398	likely_pathogenic	0.6038	pathogenic	-0.314	Destabilizing	0.988	D	0.593	neutral	D	0.624734984	None	None	I
P/S	0.4145	ambiguous	0.3266	benign	-1.084	Destabilizing	0.11	N	0.27	neutral	D	0.575839323	None	None	I
P/T	0.4577	ambiguous	0.3673	ambiguous	-0.974	Destabilizing	0.414	N	0.463	neutral	D	0.598995068	None	None	I
P/V	0.6418	likely_pathogenic	0.503	ambiguous	-0.569	Destabilizing	0.569	D	0.542	neutral	None	None	None	None	I
P/W	0.9586	likely_pathogenic	0.945	pathogenic	-0.927	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
P/Y	0.883	likely_pathogenic	0.8337	pathogenic	-0.617	Destabilizing	0.997	D	0.668	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.