TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33733	101422;101423;101424	chr2:178535418;178535417;178535416	chr2:179400145;179400144;179400143
N2AB	32092	96499;96500;96501	chr2:178535418;178535417;178535416	chr2:179400145;179400144;179400143
N2A	31165	93718;93719;93720	chr2:178535418;178535417;178535416	chr2:179400145;179400144;179400143
N2B	24668	74227;74228;74229	chr2:178535418;178535417;178535416	chr2:179400145;179400144;179400143
Novex-1	24793	74602;74603;74604	chr2:178535418;178535417;178535416	chr2:179400145;179400144;179400143
Novex-2	24860	74803;74804;74805	chr2:178535418;178535417;178535416	chr2:179400145;179400144;179400143
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: Fn3-132
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3915
• 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/V	None	None	0.883	N	0.387	0.205	0.371344866733	gnomAD-4.0.0	3.18238E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88352E-05	0	2.85807E-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	0.7725	likely_pathogenic	0.6811	pathogenic	-0.658	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	N
A/D	0.8559	likely_pathogenic	0.6984	pathogenic	-0.585	Destabilizing	0.962	D	0.453	neutral	None	None	None	None	N
A/E	0.809	likely_pathogenic	0.619	pathogenic	-0.754	Destabilizing	0.964	D	0.399	neutral	N	0.433745407	None	None	N
A/F	0.841	likely_pathogenic	0.7179	pathogenic	-0.945	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
A/G	0.2065	likely_benign	0.1879	benign	-0.154	Destabilizing	0.002	N	0.241	neutral	N	0.388415762	None	None	N
A/H	0.8789	likely_pathogenic	0.7975	pathogenic	-0.283	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
A/I	0.8212	likely_pathogenic	0.6616	pathogenic	-0.348	Destabilizing	0.995	D	0.415	neutral	None	None	None	None	N
A/K	0.9318	likely_pathogenic	0.8489	pathogenic	-0.487	Destabilizing	0.989	D	0.403	neutral	None	None	None	None	N
A/L	0.5731	likely_pathogenic	0.4098	ambiguous	-0.348	Destabilizing	0.964	D	0.413	neutral	None	None	None	None	N
A/M	0.6409	likely_pathogenic	0.473	ambiguous	-0.362	Destabilizing	1.0	D	0.465	neutral	None	None	None	None	N
A/N	0.6475	likely_pathogenic	0.4919	ambiguous	-0.137	Destabilizing	0.747	D	0.492	neutral	None	None	None	None	N
A/P	0.9036	likely_pathogenic	0.835	pathogenic	-0.255	Destabilizing	0.975	D	0.421	neutral	N	0.41354628	None	None	N
A/Q	0.7282	likely_pathogenic	0.6032	pathogenic	-0.444	Destabilizing	0.995	D	0.413	neutral	None	None	None	None	N
A/R	0.8739	likely_pathogenic	0.7714	pathogenic	-0.042	Destabilizing	0.989	D	0.415	neutral	None	None	None	None	N
A/S	0.11	likely_benign	0.0938	benign	-0.269	Destabilizing	0.005	N	0.249	neutral	N	0.367309771	None	None	N
A/T	0.2433	likely_benign	0.148	benign	-0.372	Destabilizing	0.64	D	0.347	neutral	N	0.402923854	None	None	N
A/V	0.5084	ambiguous	0.3301	benign	-0.255	Destabilizing	0.883	D	0.387	neutral	N	0.463108309	None	None	N
A/W	0.9707	likely_pathogenic	0.938	pathogenic	-1.07	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
A/Y	0.9069	likely_pathogenic	0.8175	pathogenic	-0.723	Destabilizing	0.998	D	0.524	neutral	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.