TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7350	22273;22274;22275	chr2:178722851;178722850;178722849	chr2:179587578;179587577;179587576
N2AB	7033	21322;21323;21324	chr2:178722851;178722850;178722849	chr2:179587578;179587577;179587576
N2A	6106	18541;18542;18543	chr2:178722851;178722850;178722849	chr2:179587578;179587577;179587576
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-58
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.6891
• 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/A	rs2078649611	None	0.958	D	0.544	0.674	0.505701759113	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
P/A	rs2078649611	None	0.958	D	0.544	0.674	0.505701759113	gnomAD-4.0.0	2.5642E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.68183E-05	0
P/Q	rs1467666220	None	0.999	D	0.638	0.72	0.714142150149	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/Q	rs1467666220	None	0.999	D	0.638	0.72	0.714142150149	gnomAD-4.0.0	2.56447E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.7895E-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
P/A	0.6657	likely_pathogenic	0.8452	pathogenic	-0.606	Destabilizing	0.958	D	0.544	neutral	D	0.546314149	None	None	I
P/C	0.9822	likely_pathogenic	0.9943	pathogenic	-0.633	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
P/D	0.9509	likely_pathogenic	0.981	pathogenic	-0.454	Destabilizing	0.981	D	0.639	neutral	None	None	None	None	I
P/E	0.8844	likely_pathogenic	0.9529	pathogenic	-0.576	Destabilizing	0.988	D	0.644	neutral	None	None	None	None	I
P/F	0.99	likely_pathogenic	0.997	pathogenic	-0.836	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
P/G	0.902	likely_pathogenic	0.9533	pathogenic	-0.74	Destabilizing	0.993	D	0.616	neutral	None	None	None	None	I
P/H	0.9226	likely_pathogenic	0.9757	pathogenic	-0.333	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	I
P/I	0.9637	likely_pathogenic	0.9865	pathogenic	-0.405	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
P/K	0.932	likely_pathogenic	0.9735	pathogenic	-0.561	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
P/L	0.8215	likely_pathogenic	0.9275	pathogenic	-0.405	Destabilizing	1.0	D	0.657	neutral	D	0.595294741	None	None	I
P/M	0.9469	likely_pathogenic	0.9822	pathogenic	-0.364	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
P/N	0.9518	likely_pathogenic	0.9817	pathogenic	-0.263	Destabilizing	0.997	D	0.631	neutral	None	None	None	None	I
P/Q	0.8574	likely_pathogenic	0.9522	pathogenic	-0.54	Destabilizing	0.999	D	0.638	neutral	D	0.533312003	None	None	I
P/R	0.8565	likely_pathogenic	0.9415	pathogenic	-0.001	Destabilizing	1.0	D	0.652	neutral	D	0.594891133	None	None	I
P/S	0.8256	likely_pathogenic	0.9319	pathogenic	-0.61	Destabilizing	0.934	D	0.319	neutral	D	0.54580717	None	None	I
P/T	0.7246	likely_pathogenic	0.8848	pathogenic	-0.636	Destabilizing	0.992	D	0.656	neutral	D	0.588158358	None	None	I
P/V	0.9022	likely_pathogenic	0.9586	pathogenic	-0.437	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	I
P/W	0.9905	likely_pathogenic	0.9973	pathogenic	-0.902	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
P/Y	0.984	likely_pathogenic	0.9951	pathogenic	-0.615	Destabilizing	1.0	D	0.673	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.