TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3978	12157;12158;12159	chr2:178741301;178741300;178741299	chr2:179606028;179606027;179606026
N2AB	3661	11206;11207;11208	chr2:178741301;178741300;178741299	chr2:179606028;179606027;179606026
N2A	None	None	chr2:None	chr2:None
N2B	3615	11068;11069;11070	chr2:178741301;178741300;178741299	chr2:179606028;179606027;179606026
Novex-1	3740	11443;11444;11445	chr2:178741301;178741300;178741299	chr2:179606028;179606027;179606026
Novex-2	3807	11644;11645;11646	chr2:178741301;178741300;178741299	chr2:179606028;179606027;179606026
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-28
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1816
• Predicted PPI site: I

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	rs1472692011	-1.429	0.968	D	0.609	0.534	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/F	rs1472692011	-1.429	0.968	D	0.609	0.534	None	gnomAD-4.0.0	1.59108E-06	None	None	None	None	I	None	0	2.28634E-05	None	0	0	None	0	0	0	0	0
L/P	None	None	0.995	D	0.772	0.725	None	gnomAD-4.0.0	8.40225E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.18751E-06	0	0
L/R	None	None	0.995	D	0.725	0.715	None	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	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	0.7921	likely_pathogenic	0.7655	pathogenic	-2.164	Highly Destabilizing	0.919	D	0.591	neutral	None	None	None	None	I
L/C	0.8259	likely_pathogenic	0.8127	pathogenic	-1.376	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
L/D	0.9823	likely_pathogenic	0.9806	pathogenic	-2.68	Highly Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	I
L/E	0.9119	likely_pathogenic	0.8964	pathogenic	-2.413	Highly Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	I
L/F	0.3784	ambiguous	0.3682	ambiguous	-1.42	Destabilizing	0.968	D	0.609	neutral	D	0.607983544	None	None	I
L/G	0.9429	likely_pathogenic	0.9382	pathogenic	-2.674	Highly Destabilizing	0.996	D	0.744	deleterious	None	None	None	None	I
L/H	0.7764	likely_pathogenic	0.7599	pathogenic	-2.213	Highly Destabilizing	0.999	D	0.758	deleterious	D	0.752706044	None	None	I
L/I	0.1182	likely_benign	0.1118	benign	-0.66	Destabilizing	0.011	N	0.209	neutral	N	0.469810259	None	None	I
L/K	0.844	likely_pathogenic	0.8298	pathogenic	-1.629	Destabilizing	0.988	D	0.711	prob.delet.	None	None	None	None	I
L/M	0.288	likely_benign	0.2682	benign	-0.67	Destabilizing	0.976	D	0.647	neutral	None	None	None	None	I
L/N	0.9211	likely_pathogenic	0.9169	pathogenic	-2.164	Highly Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	I
L/P	0.8887	likely_pathogenic	0.8958	pathogenic	-1.149	Destabilizing	0.995	D	0.772	deleterious	D	0.65436035	None	None	I
L/Q	0.7393	likely_pathogenic	0.7029	pathogenic	-1.916	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	I
L/R	0.7157	likely_pathogenic	0.694	pathogenic	-1.649	Destabilizing	0.995	D	0.725	prob.delet.	D	0.676680096	None	None	I
L/S	0.9164	likely_pathogenic	0.909	pathogenic	-2.736	Highly Destabilizing	0.988	D	0.679	prob.neutral	None	None	None	None	I
L/T	0.8237	likely_pathogenic	0.7965	pathogenic	-2.314	Highly Destabilizing	0.919	D	0.636	neutral	None	None	None	None	I
L/V	0.176	likely_benign	0.1564	benign	-1.149	Destabilizing	0.103	N	0.261	neutral	N	0.516502007	None	None	I
L/W	0.6972	likely_pathogenic	0.6824	pathogenic	-1.743	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
L/Y	0.7382	likely_pathogenic	0.7438	pathogenic	-1.427	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	I

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.