TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6059	18400;18401;18402	chr2:178730225;178730224;178730223	chr2:179594952;179594951;179594950
N2AB	5742	17449;17450;17451	chr2:178730225;178730224;178730223	chr2:179594952;179594951;179594950
N2A	4815	14668;14669;14670	chr2:178730225;178730224;178730223	chr2:179594952;179594951;179594950
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-44
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2851
• 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
S/L	None	None	0.978	N	0.491	0.318	0.681597050132	gnomAD-4.0.0	2.05306E-06	None	None	None	None	N	None	0	0	None	3.82907E-05	0	None	0	0	1.79911E-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
S/A	0.1023	likely_benign	0.1049	benign	-0.925	Destabilizing	0.973	D	0.338	neutral	N	0.487748542	None	None	N
S/C	0.1907	likely_benign	0.2075	benign	-0.641	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
S/D	0.5846	likely_pathogenic	0.6905	pathogenic	0.187	Stabilizing	1.0	D	0.521	neutral	None	None	None	None	N
S/E	0.6618	likely_pathogenic	0.7434	pathogenic	0.179	Stabilizing	0.999	D	0.469	neutral	None	None	None	None	N
S/F	0.2593	likely_benign	0.2488	benign	-1.149	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
S/G	0.1716	likely_benign	0.1888	benign	-1.142	Destabilizing	0.999	D	0.41	neutral	None	None	None	None	N
S/H	0.4202	ambiguous	0.4646	ambiguous	-1.482	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
S/I	0.2238	likely_benign	0.2572	benign	-0.45	Destabilizing	0.983	D	0.534	neutral	None	None	None	None	N
S/K	0.7469	likely_pathogenic	0.8322	pathogenic	-0.479	Destabilizing	0.999	D	0.472	neutral	None	None	None	None	N
S/L	0.1248	likely_benign	0.1361	benign	-0.45	Destabilizing	0.978	D	0.491	neutral	N	0.491327565	None	None	N
S/M	0.2495	likely_benign	0.2594	benign	-0.203	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
S/N	0.1951	likely_benign	0.2441	benign	-0.385	Destabilizing	1.0	D	0.53	neutral	None	None	None	None	N
S/P	0.8599	likely_pathogenic	0.8976	pathogenic	-0.577	Destabilizing	0.999	D	0.675	neutral	N	0.489962425	None	None	N
S/Q	0.5964	likely_pathogenic	0.6499	pathogenic	-0.587	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
S/R	0.6449	likely_pathogenic	0.7377	pathogenic	-0.369	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
S/T	0.1133	likely_benign	0.1239	benign	-0.546	Destabilizing	0.989	D	0.42	neutral	N	0.495098589	None	None	N
S/V	0.2281	likely_benign	0.2491	benign	-0.577	Destabilizing	0.611	D	0.37	neutral	None	None	None	None	N
S/W	0.4076	ambiguous	0.3839	ambiguous	-1.016	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
S/Y	0.2111	likely_benign	0.2036	benign	-0.777	Destabilizing	1.0	D	0.704	prob.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.