TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7459	22600;22601;22602	chr2:178722412;178722411;178722410	chr2:179587139;179587138;179587137
N2AB	7142	21649;21650;21651	chr2:178722412;178722411;178722410	chr2:179587139;179587138;179587137
N2A	6215	18868;18869;18870	chr2:178722412;178722411;178722410	chr2:179587139;179587138;179587137
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-59
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2385
• 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/S	None	None	0.996	D	0.719	0.577	0.890862651804	gnomAD-4.0.0	1.59201E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85987E-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	0.7437	likely_pathogenic	0.7136	pathogenic	-1.864	Destabilizing	0.978	D	0.499	neutral	None	None	None	None	N
L/C	0.8448	likely_pathogenic	0.8154	pathogenic	-0.958	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
L/D	0.9863	likely_pathogenic	0.9835	pathogenic	-1.933	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
L/E	0.8716	likely_pathogenic	0.8539	pathogenic	-1.706	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
L/F	0.3843	ambiguous	0.3711	ambiguous	-1.113	Destabilizing	0.989	D	0.583	neutral	D	0.527116577	None	None	N
L/G	0.9447	likely_pathogenic	0.9369	pathogenic	-2.353	Highly Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
L/H	0.7454	likely_pathogenic	0.735	pathogenic	-1.664	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/I	0.1105	likely_benign	0.1067	benign	-0.465	Destabilizing	0.026	N	0.4	neutral	N	0.45452419	None	None	N
L/K	0.8312	likely_pathogenic	0.818	pathogenic	-1.247	Destabilizing	0.948	D	0.734	prob.delet.	None	None	None	None	N
L/M	0.2431	likely_benign	0.2295	benign	-0.369	Destabilizing	0.987	D	0.62	neutral	None	None	None	None	N
L/N	0.9333	likely_pathogenic	0.9236	pathogenic	-1.67	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
L/P	0.9356	likely_pathogenic	0.9258	pathogenic	-0.912	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
L/Q	0.5484	ambiguous	0.5435	ambiguous	-1.5	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
L/R	0.6907	likely_pathogenic	0.6884	pathogenic	-1.107	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
L/S	0.8705	likely_pathogenic	0.8523	pathogenic	-2.313	Highly Destabilizing	0.996	D	0.719	prob.delet.	D	0.559299389	None	None	N
L/T	0.7656	likely_pathogenic	0.7292	pathogenic	-1.936	Destabilizing	0.989	D	0.641	neutral	None	None	None	None	N
L/V	0.1347	likely_benign	0.1314	benign	-0.912	Destabilizing	0.008	N	0.266	neutral	N	0.502240779	None	None	N
L/W	0.6829	likely_pathogenic	0.6676	pathogenic	-1.425	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/Y	0.7957	likely_pathogenic	0.7858	pathogenic	-1.059	Destabilizing	0.967	D	0.708	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.