TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4781	14566;14567;14568	chr2:178738112;178738111;178738110	chr2:179602839;179602838;179602837
N2AB	4464	13615;13616;13617	chr2:178738112;178738111;178738110	chr2:179602839;179602838;179602837
N2A	3537	10834;10835;10836	chr2:178738112;178738111;178738110	chr2:179602839;179602838;179602837
N2B	4418	13477;13478;13479	chr2:178738112;178738111;178738110	chr2:179602839;179602838;179602837
Novex-1	4543	13852;13853;13854	chr2:178738112;178738111;178738110	chr2:179602839;179602838;179602837
Novex-2	4610	14053;14054;14055	chr2:178738112;178738111;178738110	chr2:179602839;179602838;179602837
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-30
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1937
• 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
V/I	rs2081852478	None	0.549	N	0.486	0.204	0.594113984522	gnomAD-4.0.0	1.59172E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85925E-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
V/A	0.1137	likely_benign	0.1289	benign	-1.014	Destabilizing	0.002	N	0.117	neutral	N	0.454873783	None	None	I
V/C	0.7859	likely_pathogenic	0.8126	pathogenic	-0.83	Destabilizing	0.977	D	0.55	neutral	None	None	None	None	I
V/D	0.2841	likely_benign	0.3611	ambiguous	-0.397	Destabilizing	0.002	N	0.403	neutral	N	0.45679289	None	None	I
V/E	0.3252	likely_benign	0.4289	ambiguous	-0.457	Destabilizing	0.021	N	0.375	neutral	None	None	None	None	I
V/F	0.2711	likely_benign	0.3365	benign	-0.907	Destabilizing	0.896	D	0.583	neutral	D	0.647606971	None	None	I
V/G	0.2972	likely_benign	0.3651	ambiguous	-1.247	Destabilizing	0.379	N	0.625	neutral	D	0.591557029	None	None	I
V/H	0.718	likely_pathogenic	0.7878	pathogenic	-0.706	Destabilizing	0.972	D	0.669	neutral	None	None	None	None	I
V/I	0.0973	likely_benign	0.1146	benign	-0.517	Destabilizing	0.549	D	0.486	neutral	N	0.500102074	None	None	I
V/K	0.5138	ambiguous	0.6408	pathogenic	-0.747	Destabilizing	0.617	D	0.639	neutral	None	None	None	None	I
V/L	0.3126	likely_benign	0.4025	ambiguous	-0.517	Destabilizing	0.201	N	0.473	neutral	D	0.537617579	None	None	I
V/M	0.1982	likely_benign	0.2487	benign	-0.474	Destabilizing	0.972	D	0.543	neutral	None	None	None	None	I
V/N	0.3318	likely_benign	0.4026	ambiguous	-0.487	Destabilizing	0.617	D	0.687	prob.neutral	None	None	None	None	I
V/P	0.9541	likely_pathogenic	0.9692	pathogenic	-0.646	Destabilizing	0.92	D	0.658	neutral	None	None	None	None	I
V/Q	0.4381	ambiguous	0.5312	ambiguous	-0.698	Destabilizing	0.85	D	0.656	neutral	None	None	None	None	I
V/R	0.4746	ambiguous	0.5928	pathogenic	-0.234	Destabilizing	0.85	D	0.685	prob.neutral	None	None	None	None	I
V/S	0.1874	likely_benign	0.2202	benign	-1.009	Destabilizing	0.447	N	0.612	neutral	None	None	None	None	I
V/T	0.1628	likely_benign	0.1812	benign	-0.957	Destabilizing	0.617	D	0.453	neutral	None	None	None	None	I
V/W	0.9192	likely_pathogenic	0.9528	pathogenic	-0.98	Destabilizing	0.992	D	0.707	prob.neutral	None	None	None	None	I
V/Y	0.686	likely_pathogenic	0.7512	pathogenic	-0.697	Destabilizing	0.972	D	0.585	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.