TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10132	30619;30620;30621	chr2:178702493;178702492;178702491	chr2:179567220;179567219;179567218
N2AB	9815	29668;29669;29670	chr2:178702493;178702492;178702491	chr2:179567220;179567219;179567218
N2A	8888	26887;26888;26889	chr2:178702493;178702492;178702491	chr2:179567220;179567219;179567218
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-86
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1515
• 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
H/L	None	None	0.942	None	0.801	0.431	0.611858120693	gnomAD-4.0.0	3.42068E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49694E-06	0	0
H/R	rs1057518758	-1.46	0.97	None	0.741	0.397	0.331365685468	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
H/R	rs1057518758	-1.46	0.97	None	0.741	0.397	0.331365685468	gnomAD-4.0.0	6.84137E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87259E-05	0	0	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
H/A	0.9939	likely_pathogenic	0.992	pathogenic	-1.911	Destabilizing	0.86	D	0.771	deleterious	None	None	None	None	N
H/C	0.873	likely_pathogenic	0.8611	pathogenic	-1.153	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
H/D	0.9974	likely_pathogenic	0.9967	pathogenic	-2.041	Highly Destabilizing	0.904	D	0.793	deleterious	None	None	None	None	N
H/E	0.9978	likely_pathogenic	0.9973	pathogenic	-1.831	Destabilizing	0.86	D	0.725	prob.delet.	None	None	None	None	N
H/F	0.9544	likely_pathogenic	0.9557	pathogenic	0.146	Stabilizing	0.993	D	0.802	deleterious	None	None	None	None	N
H/G	0.996	likely_pathogenic	0.9958	pathogenic	-2.332	Highly Destabilizing	0.86	D	0.777	deleterious	None	None	None	None	N
H/I	0.9928	likely_pathogenic	0.9922	pathogenic	-0.645	Destabilizing	0.978	D	0.848	deleterious	None	None	None	None	N
H/K	0.9882	likely_pathogenic	0.9855	pathogenic	-1.122	Destabilizing	0.86	D	0.792	deleterious	None	None	None	None	N
H/L	0.9464	likely_pathogenic	0.9357	pathogenic	-0.645	Destabilizing	0.942	D	0.801	deleterious	None	None	None	None	N
H/M	0.9935	likely_pathogenic	0.9925	pathogenic	-0.878	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
H/N	0.9533	likely_pathogenic	0.9515	pathogenic	-1.945	Destabilizing	0.904	D	0.732	prob.delet.	None	None	None	None	N
H/P	0.9955	likely_pathogenic	0.9964	pathogenic	-1.061	Destabilizing	0.014	N	0.669	neutral	None	None	None	None	N
H/Q	0.9817	likely_pathogenic	0.9753	pathogenic	-1.524	Destabilizing	0.97	D	0.754	deleterious	None	None	None	None	N
H/R	0.9372	likely_pathogenic	0.921	pathogenic	-1.269	Destabilizing	0.97	D	0.741	deleterious	None	None	None	None	N
H/S	0.9798	likely_pathogenic	0.9773	pathogenic	-2.08	Highly Destabilizing	0.86	D	0.791	deleterious	None	None	None	None	N
H/T	0.9932	likely_pathogenic	0.992	pathogenic	-1.751	Destabilizing	0.956	D	0.774	deleterious	None	None	None	None	N
H/V	0.9902	likely_pathogenic	0.9893	pathogenic	-1.061	Destabilizing	0.978	D	0.809	deleterious	None	None	None	None	N
H/W	0.9544	likely_pathogenic	0.9545	pathogenic	0.738	Stabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
H/Y	0.8441	likely_pathogenic	0.8381	pathogenic	0.462	Stabilizing	0.99	D	0.736	prob.delet.	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.