TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31084	93475;93476;93477	chr2:178548376;178548375;178548374	chr2:179413103;179413102;179413101
N2AB	29443	88552;88553;88554	chr2:178548376;178548375;178548374	chr2:179413103;179413102;179413101
N2A	28516	85771;85772;85773	chr2:178548376;178548375;178548374	chr2:179413103;179413102;179413101
N2B	22019	66280;66281;66282	chr2:178548376;178548375;178548374	chr2:179413103;179413102;179413101
Novex-1	22144	66655;66656;66657	chr2:178548376;178548375;178548374	chr2:179413103;179413102;179413101
Novex-2	22211	66856;66857;66858	chr2:178548376;178548375;178548374	chr2:179413103;179413102;179413101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-114
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1979
• 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
V/D	None	None	0.484	N	0.56	0.362	0.706306783786	gnomAD-4.0.0	6.84184E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6564E-05

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	0.1618	likely_benign	0.1518	benign	-1.372	Destabilizing	None	N	0.261	neutral	N	0.39447773	None	None	N
V/C	0.5822	likely_pathogenic	0.5833	pathogenic	-0.796	Destabilizing	0.824	D	0.464	neutral	None	None	None	None	N
V/D	0.4335	ambiguous	0.3946	ambiguous	-1.123	Destabilizing	0.484	N	0.56	neutral	N	0.488428041	None	None	N
V/E	0.3361	likely_benign	0.3115	benign	-1.106	Destabilizing	0.38	N	0.479	neutral	None	None	None	None	N
V/F	0.152	likely_benign	0.1558	benign	-1.018	Destabilizing	0.317	N	0.467	neutral	N	0.518404231	None	None	N
V/G	0.2138	likely_benign	0.2039	benign	-1.7	Destabilizing	0.188	N	0.509	neutral	N	0.410217973	None	None	N
V/H	0.4957	ambiguous	0.4591	ambiguous	-1.21	Destabilizing	0.935	D	0.545	neutral	None	None	None	None	N
V/I	0.0673	likely_benign	0.0693	benign	-0.57	Destabilizing	None	N	0.242	neutral	N	0.451256519	None	None	N
V/K	0.3969	ambiguous	0.3476	ambiguous	-1.11	Destabilizing	0.38	N	0.451	neutral	None	None	None	None	N
V/L	0.1436	likely_benign	0.1477	benign	-0.57	Destabilizing	None	N	0.147	neutral	N	0.450813802	None	None	N
V/M	0.0955	likely_benign	0.0976	benign	-0.434	Destabilizing	0.035	N	0.4	neutral	None	None	None	None	N
V/N	0.1989	likely_benign	0.1948	benign	-0.932	Destabilizing	0.555	D	0.563	neutral	None	None	None	None	N
V/P	0.8548	likely_pathogenic	0.841	pathogenic	-0.802	Destabilizing	0.555	D	0.511	neutral	None	None	None	None	N
V/Q	0.2733	likely_benign	0.2523	benign	-1.064	Destabilizing	0.555	D	0.506	neutral	None	None	None	None	N
V/R	0.3949	ambiguous	0.3499	ambiguous	-0.625	Destabilizing	0.38	N	0.564	neutral	None	None	None	None	N
V/S	0.1612	likely_benign	0.1488	benign	-1.446	Destabilizing	0.081	N	0.439	neutral	None	None	None	None	N
V/T	0.1463	likely_benign	0.1342	benign	-1.314	Destabilizing	0.149	N	0.447	neutral	None	None	None	None	N
V/W	0.7843	likely_pathogenic	0.7808	pathogenic	-1.237	Destabilizing	0.935	D	0.596	neutral	None	None	None	None	N
V/Y	0.4563	ambiguous	0.4488	ambiguous	-0.919	Destabilizing	0.555	D	0.481	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.