TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22625	68098;68099;68100	chr2:178579157;178579156;178579155	chr2:179443884;179443883;179443882
N2AB	20984	63175;63176;63177	chr2:178579157;178579156;178579155	chr2:179443884;179443883;179443882
N2A	20057	60394;60395;60396	chr2:178579157;178579156;178579155	chr2:179443884;179443883;179443882
N2B	13560	40903;40904;40905	chr2:178579157;178579156;178579155	chr2:179443884;179443883;179443882
Novex-1	13685	41278;41279;41280	chr2:178579157;178579156;178579155	chr2:179443884;179443883;179443882
Novex-2	13752	41479;41480;41481	chr2:178579157;178579156;178579155	chr2:179443884;179443883;179443882
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-127
• Domain position: 66
• Structural Position: 158
• Q(SASA): 0.1507
• 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/V	rs753627819	-1.2	0.543	N	0.339	0.174	0.527857482506	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
L/V	rs753627819	-1.2	0.543	N	0.339	0.174	0.527857482506	gnomAD-4.0.0	1.59208E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85989E-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	0.5352	ambiguous	0.4669	ambiguous	-2.149	Highly Destabilizing	0.611	D	0.457	neutral	None	None	None	None	I
L/C	0.7463	likely_pathogenic	0.7311	pathogenic	-1.625	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
L/D	0.9995	likely_pathogenic	0.9993	pathogenic	-1.878	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	I
L/E	0.9956	likely_pathogenic	0.9938	pathogenic	-1.807	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
L/F	0.8571	likely_pathogenic	0.843	pathogenic	-1.499	Destabilizing	0.998	D	0.719	prob.delet.	N	0.502671402	None	None	I
L/G	0.9312	likely_pathogenic	0.9121	pathogenic	-2.553	Highly Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	I
L/H	0.9941	likely_pathogenic	0.9926	pathogenic	-1.844	Destabilizing	1.0	D	0.793	deleterious	N	0.514699271	None	None	I
L/I	0.2591	likely_benign	0.2317	benign	-1.062	Destabilizing	0.978	D	0.603	neutral	N	0.482032252	None	None	I
L/K	0.9959	likely_pathogenic	0.995	pathogenic	-1.541	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	I
L/M	0.3648	ambiguous	0.3158	benign	-0.966	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
L/N	0.9954	likely_pathogenic	0.9936	pathogenic	-1.493	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
L/P	0.9977	likely_pathogenic	0.997	pathogenic	-1.397	Destabilizing	0.998	D	0.805	deleterious	N	0.514445782	None	None	I
L/Q	0.9773	likely_pathogenic	0.9688	pathogenic	-1.605	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
L/R	0.9865	likely_pathogenic	0.9851	pathogenic	-1.032	Destabilizing	0.998	D	0.775	deleterious	N	0.514445782	None	None	I
L/S	0.9469	likely_pathogenic	0.9226	pathogenic	-2.188	Highly Destabilizing	0.995	D	0.774	deleterious	None	None	None	None	I
L/T	0.8498	likely_pathogenic	0.8028	pathogenic	-1.989	Destabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	I
L/V	0.1543	likely_benign	0.1445	benign	-1.397	Destabilizing	0.543	D	0.339	neutral	N	0.437255433	None	None	I
L/W	0.9916	likely_pathogenic	0.99	pathogenic	-1.648	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
L/Y	0.9884	likely_pathogenic	0.9856	pathogenic	-1.407	Destabilizing	1.0	D	0.735	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.