TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24538	73837;73838;73839	chr2:178572520;178572519;178572518	chr2:179437247;179437246;179437245
N2AB	22897	68914;68915;68916	chr2:178572520;178572519;178572518	chr2:179437247;179437246;179437245
N2A	21970	66133;66134;66135	chr2:178572520;178572519;178572518	chr2:179437247;179437246;179437245
N2B	15473	46642;46643;46644	chr2:178572520;178572519;178572518	chr2:179437247;179437246;179437245
Novex-1	15598	47017;47018;47019	chr2:178572520;178572519;178572518	chr2:179437247;179437246;179437245
Novex-2	15665	47218;47219;47220	chr2:178572520;178572519;178572518	chr2:179437247;179437246;179437245
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-66
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1121
• 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
L/P	None	None	1.0	D	0.93	0.721	0.799372495493	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
L/A	0.9436	likely_pathogenic	0.9248	pathogenic	-2.677	Highly Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
L/C	0.9231	likely_pathogenic	0.9044	pathogenic	-1.735	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9998	pathogenic	-3.3	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
L/E	0.9987	likely_pathogenic	0.9984	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/F	0.7638	likely_pathogenic	0.6788	pathogenic	-1.606	Destabilizing	0.998	D	0.728	prob.delet.	D	0.564008379	None	None	N
L/G	0.9963	likely_pathogenic	0.9947	pathogenic	-3.309	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/H	0.9973	likely_pathogenic	0.996	pathogenic	-3.1	Highly Destabilizing	1.0	D	0.904	deleterious	D	0.565275826	None	None	N
L/I	0.0823	likely_benign	0.0839	benign	-0.772	Destabilizing	0.147	N	0.339	neutral	N	0.494842299	None	None	N
L/K	0.9977	likely_pathogenic	0.9974	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/M	0.309	likely_benign	0.2698	benign	-0.896	Destabilizing	0.994	D	0.705	prob.neutral	None	None	None	None	N
L/N	0.9988	likely_pathogenic	0.9983	pathogenic	-2.779	Highly Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
L/P	0.9981	likely_pathogenic	0.9977	pathogenic	-1.398	Destabilizing	1.0	D	0.93	deleterious	D	0.565275826	None	None	N
L/Q	0.9952	likely_pathogenic	0.9935	pathogenic	-2.367	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/R	0.9958	likely_pathogenic	0.9948	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.565275826	None	None	N
L/S	0.9964	likely_pathogenic	0.9944	pathogenic	-3.324	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/T	0.9752	likely_pathogenic	0.9683	pathogenic	-2.809	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/V	0.1072	likely_benign	0.1065	benign	-1.398	Destabilizing	0.69	D	0.629	neutral	D	0.524660987	None	None	N
L/W	0.9912	likely_pathogenic	0.9842	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/Y	0.989	likely_pathogenic	0.9825	pathogenic	-1.786	Destabilizing	1.0	D	0.808	deleterious	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.