TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14835	44728;44729;44730	chr2:178625318;178625317;178625316	chr2:179490045;179490044;179490043
N2AB	13194	39805;39806;39807	chr2:178625318;178625317;178625316	chr2:179490045;179490044;179490043
N2A	12267	37024;37025;37026	chr2:178625318;178625317;178625316	chr2:179490045;179490044;179490043
N2B	5770	17533;17534;17535	chr2:178625318;178625317;178625316	chr2:179490045;179490044;179490043
Novex-1	5895	17908;17909;17910	chr2:178625318;178625317;178625316	chr2:179490045;179490044;179490043
Novex-2	5962	18109;18110;18111	chr2:178625318;178625317;178625316	chr2:179490045;179490044;179490043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-99
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0428
• 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/I	None	None	0.884	N	0.375	0.093	0.188950314367	gnomAD-4.0.0	1.3741E-06	None	None	None	None	N	None	3.03306E-05	0	None	0	0	None	0	0	0	0	1.66384E-05
L/Q	rs1559907686	None	1.0	N	0.929	0.44	0.696656391576	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	1.26711E-04	0	None	0	0	None	0	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
L/A	0.8371	likely_pathogenic	0.8574	pathogenic	-2.764	Highly Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
L/C	0.6996	likely_pathogenic	0.7002	pathogenic	-1.775	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/D	0.9982	likely_pathogenic	0.999	pathogenic	-3.504	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/E	0.989	likely_pathogenic	0.9929	pathogenic	-3.196	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/F	0.4678	ambiguous	0.606	pathogenic	-1.675	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/G	0.9676	likely_pathogenic	0.9735	pathogenic	-3.344	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/H	0.9678	likely_pathogenic	0.9826	pathogenic	-3.027	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/I	0.1515	likely_benign	0.1883	benign	-1.017	Destabilizing	0.884	D	0.375	neutral	N	0.447263231	None	None	N
L/K	0.9801	likely_pathogenic	0.9863	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/M	0.2277	likely_benign	0.2854	benign	-1.082	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/N	0.9868	likely_pathogenic	0.9908	pathogenic	-2.775	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/P	0.9925	likely_pathogenic	0.9964	pathogenic	-1.591	Destabilizing	1.0	D	0.925	deleterious	N	0.47619935	None	None	N
L/Q	0.9528	likely_pathogenic	0.9677	pathogenic	-2.461	Highly Destabilizing	1.0	D	0.929	deleterious	N	0.47619935	None	None	N
L/R	0.9585	likely_pathogenic	0.9695	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.922	deleterious	N	0.47619935	None	None	N
L/S	0.9796	likely_pathogenic	0.9862	pathogenic	-3.295	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/T	0.9232	likely_pathogenic	0.9433	pathogenic	-2.838	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/V	0.1592	likely_benign	0.1785	benign	-1.591	Destabilizing	0.981	D	0.675	prob.neutral	N	0.43484045	None	None	N
L/W	0.9172	likely_pathogenic	0.9514	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/Y	0.9079	likely_pathogenic	0.9448	pathogenic	-1.899	Destabilizing	1.0	D	0.868	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.