TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6379	19360;19361;19362	chr2:178728903;178728902;178728901	chr2:179593630;179593629;179593628
N2AB	6062	18409;18410;18411	chr2:178728903;178728902;178728901	chr2:179593630;179593629;179593628
N2A	5135	15628;15629;15630	chr2:178728903;178728902;178728901	chr2:179593630;179593629;179593628
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-47
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0935
• 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/F	rs1448772446	-1.776	1.0	D	0.839	0.568	0.741748209757	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	3.02E-05	None	0	0	None	0	None	0	0	0
L/F	rs1448772446	-1.776	1.0	D	0.839	0.568	0.741748209757	gnomAD-4.0.0	1.38444E-06	None	None	None	None	N	None	0	2.30926E-05	None	0	0	None	0	0	9.07538E-07	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	0.9432	likely_pathogenic	0.9381	pathogenic	-2.609	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
L/C	0.9182	likely_pathogenic	0.9043	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9995	pathogenic	-2.496	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/E	0.9967	likely_pathogenic	0.9959	pathogenic	-2.229	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/F	0.6565	likely_pathogenic	0.676	pathogenic	-1.561	Destabilizing	1.0	D	0.839	deleterious	D	0.523592679	None	None	N
L/G	0.9912	likely_pathogenic	0.9907	pathogenic	-3.203	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/H	0.9835	likely_pathogenic	0.9799	pathogenic	-2.617	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.564195735	None	None	N
L/I	0.2441	likely_benign	0.2206	benign	-0.874	Destabilizing	0.999	D	0.579	neutral	N	0.511245188	None	None	N
L/K	0.9959	likely_pathogenic	0.9948	pathogenic	-1.835	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/M	0.4084	ambiguous	0.3996	ambiguous	-0.971	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/N	0.9957	likely_pathogenic	0.995	pathogenic	-2.252	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/P	0.9969	likely_pathogenic	0.9969	pathogenic	-1.435	Destabilizing	1.0	D	0.916	deleterious	D	0.564195735	None	None	N
L/Q	0.9776	likely_pathogenic	0.971	pathogenic	-2.026	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/R	0.9878	likely_pathogenic	0.9848	pathogenic	-1.71	Destabilizing	1.0	D	0.928	deleterious	D	0.564195735	None	None	N
L/S	0.9853	likely_pathogenic	0.9833	pathogenic	-3.066	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
L/T	0.9588	likely_pathogenic	0.9522	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/V	0.2642	likely_benign	0.233	benign	-1.435	Destabilizing	0.999	D	0.574	neutral	N	0.474410659	None	None	N
L/W	0.9741	likely_pathogenic	0.9741	pathogenic	-1.863	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/Y	0.9753	likely_pathogenic	0.9762	pathogenic	-1.6	Destabilizing	1.0	D	0.903	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.