TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30953	93082;93083;93084	chr2:178548769;178548768;178548767	chr2:179413496;179413495;179413494
N2AB	29312	88159;88160;88161	chr2:178548769;178548768;178548767	chr2:179413496;179413495;179413494
N2A	28385	85378;85379;85380	chr2:178548769;178548768;178548767	chr2:179413496;179413495;179413494
N2B	21888	65887;65888;65889	chr2:178548769;178548768;178548767	chr2:179413496;179413495;179413494
Novex-1	22013	66262;66263;66264	chr2:178548769;178548768;178548767	chr2:179413496;179413495;179413494
Novex-2	22080	66463;66464;66465	chr2:178548769;178548768;178548767	chr2:179413496;179413495;179413494
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-150
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.5276
• 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
P/L	None	None	1.0	D	0.753	0.689	0.798201095406	gnomAD-4.0.0	1.59255E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
P/A	0.9327	likely_pathogenic	0.9077	pathogenic	-0.598	Destabilizing	1.0	D	0.725	prob.delet.	D	0.554543356	None	None	I
P/C	0.9935	likely_pathogenic	0.9911	pathogenic	-0.515	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
P/D	0.9856	likely_pathogenic	0.9807	pathogenic	-0.493	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/E	0.9807	likely_pathogenic	0.975	pathogenic	-0.63	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/F	0.9963	likely_pathogenic	0.9951	pathogenic	-0.959	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
P/G	0.9764	likely_pathogenic	0.9689	pathogenic	-0.713	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/H	0.9815	likely_pathogenic	0.9747	pathogenic	-0.353	Destabilizing	1.0	D	0.779	deleterious	D	0.627101298	None	None	I
P/I	0.9725	likely_pathogenic	0.9641	pathogenic	-0.451	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
P/K	0.9864	likely_pathogenic	0.9818	pathogenic	-0.439	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/L	0.9267	likely_pathogenic	0.9057	pathogenic	-0.451	Destabilizing	1.0	D	0.753	deleterious	D	0.611081937	None	None	I
P/M	0.9803	likely_pathogenic	0.9735	pathogenic	-0.291	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
P/N	0.9816	likely_pathogenic	0.9769	pathogenic	-0.108	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/Q	0.9743	likely_pathogenic	0.9639	pathogenic	-0.427	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/R	0.9741	likely_pathogenic	0.9655	pathogenic	0.131	Stabilizing	1.0	D	0.778	deleterious	D	0.62669769	None	None	I
P/S	0.9767	likely_pathogenic	0.9663	pathogenic	-0.433	Destabilizing	1.0	D	0.741	deleterious	D	0.554036377	None	None	I
P/T	0.944	likely_pathogenic	0.9239	pathogenic	-0.479	Destabilizing	1.0	D	0.74	deleterious	D	0.62669769	None	None	I
P/V	0.9537	likely_pathogenic	0.9382	pathogenic	-0.466	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/W	0.9982	likely_pathogenic	0.9976	pathogenic	-1.011	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
P/Y	0.9935	likely_pathogenic	0.9914	pathogenic	-0.71	Destabilizing	1.0	D	0.801	deleterious	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.