TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29759	89500;89501;89502	chr2:178553730;178553729;178553728	chr2:179418457;179418456;179418455
N2AB	28118	84577;84578;84579	chr2:178553730;178553729;178553728	chr2:179418457;179418456;179418455
N2A	27191	81796;81797;81798	chr2:178553730;178553729;178553728	chr2:179418457;179418456;179418455
N2B	20694	62305;62306;62307	chr2:178553730;178553729;178553728	chr2:179418457;179418456;179418455
Novex-1	20819	62680;62681;62682	chr2:178553730;178553729;178553728	chr2:179418457;179418456;179418455
Novex-2	20886	62881;62882;62883	chr2:178553730;178553729;178553728	chr2:179418457;179418456;179418455
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: Fn3-105
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.94
• 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	None	None	0.022	N	0.141	0.088	0.266843984389	gnomAD-4.0.0	1.59199E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8593E-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	0.1928	likely_benign	0.195	benign	-0.379	Destabilizing	0.012	N	0.163	neutral	N	0.445597196	None	None	I
V/C	0.7509	likely_pathogenic	0.7668	pathogenic	-0.783	Destabilizing	0.993	D	0.375	neutral	None	None	None	None	I
V/D	0.5357	ambiguous	0.556	ambiguous	-0.321	Destabilizing	0.966	D	0.429	neutral	N	0.446925348	None	None	I
V/E	0.4594	ambiguous	0.4763	ambiguous	-0.427	Destabilizing	0.949	D	0.417	neutral	None	None	None	None	I
V/F	0.2659	likely_benign	0.2655	benign	-0.631	Destabilizing	0.934	D	0.401	neutral	N	0.519806953	None	None	I
V/G	0.2705	likely_benign	0.2799	benign	-0.473	Destabilizing	0.669	D	0.426	neutral	N	0.431707966	None	None	I
V/H	0.6946	likely_pathogenic	0.7147	pathogenic	0.008	Stabilizing	0.998	D	0.399	neutral	None	None	None	None	I
V/I	0.0815	likely_benign	0.0802	benign	-0.275	Destabilizing	0.022	N	0.141	neutral	N	0.436633783	None	None	I
V/K	0.5616	ambiguous	0.6094	pathogenic	-0.437	Destabilizing	0.949	D	0.415	neutral	None	None	None	None	I
V/L	0.2003	likely_benign	0.2006	benign	-0.275	Destabilizing	0.267	N	0.27	neutral	N	0.417815949	None	None	I
V/M	0.1867	likely_benign	0.1819	benign	-0.553	Destabilizing	0.325	N	0.298	neutral	None	None	None	None	I
V/N	0.3426	ambiguous	0.3753	ambiguous	-0.266	Destabilizing	0.974	D	0.417	neutral	None	None	None	None	I
V/P	0.4845	ambiguous	0.5189	ambiguous	-0.279	Destabilizing	0.974	D	0.437	neutral	None	None	None	None	I
V/Q	0.4235	ambiguous	0.462	ambiguous	-0.47	Destabilizing	0.974	D	0.425	neutral	None	None	None	None	I
V/R	0.4776	ambiguous	0.5249	ambiguous	0.04	Stabilizing	0.974	D	0.423	neutral	None	None	None	None	I
V/S	0.242	likely_benign	0.2573	benign	-0.588	Destabilizing	0.728	D	0.453	neutral	None	None	None	None	I
V/T	0.2427	likely_benign	0.2648	benign	-0.597	Destabilizing	0.842	D	0.4	neutral	None	None	None	None	I
V/W	0.8845	likely_pathogenic	0.8883	pathogenic	-0.7	Destabilizing	0.998	D	0.516	neutral	None	None	None	None	I
V/Y	0.6126	likely_pathogenic	0.6485	pathogenic	-0.423	Destabilizing	0.991	D	0.391	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.