TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3296	10111;10112;10113	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354
N2AB	3296	10111;10112;10113	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354
N2A	3296	10111;10112;10113	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354
N2B	3250	9973;9974;9975	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354
Novex-1	3250	9973;9974;9975	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354
Novex-2	3250	9973;9974;9975	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354
Novex-3	3296	10111;10112;10113	chr2:178764629;178764628;178764627	chr2:179629356;179629355;179629354

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-23
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0802
• 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	rs1449589213	-1.599	0.993	D	0.761	0.614	0.87793777064	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
L/F	rs1449589213	-1.599	0.993	D	0.761	0.614	0.87793777064	gnomAD-4.0.0	3.18099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85647E-06	1.43275E-05	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	0.9624	likely_pathogenic	0.9787	pathogenic	-2.028	Highly Destabilizing	0.983	D	0.759	deleterious	None	None	None	None	N
L/C	0.9544	likely_pathogenic	0.9724	pathogenic	-1.224	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-2.745	Highly Destabilizing	0.999	D	0.908	deleterious	None	None	None	None	N
L/E	0.9989	likely_pathogenic	0.9993	pathogenic	-2.458	Highly Destabilizing	0.998	D	0.889	deleterious	None	None	None	None	N
L/F	0.6808	likely_pathogenic	0.8398	pathogenic	-1.277	Destabilizing	0.993	D	0.761	deleterious	D	0.658930233	None	None	N
L/G	0.9954	likely_pathogenic	0.9975	pathogenic	-2.537	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
L/H	0.9949	likely_pathogenic	0.9977	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.74665194	None	None	N
L/I	0.4276	ambiguous	0.5567	ambiguous	-0.48	Destabilizing	0.955	D	0.663	neutral	D	0.655865731	None	None	N
L/K	0.9976	likely_pathogenic	0.9985	pathogenic	-1.516	Destabilizing	0.998	D	0.884	deleterious	None	None	None	None	N
L/M	0.4463	ambiguous	0.5991	pathogenic	-0.802	Destabilizing	0.921	D	0.589	neutral	None	None	None	None	N
L/N	0.9988	likely_pathogenic	0.9992	pathogenic	-2.265	Highly Destabilizing	0.999	D	0.907	deleterious	None	None	None	None	N
L/P	0.999	likely_pathogenic	0.9995	pathogenic	-0.991	Destabilizing	0.999	D	0.905	deleterious	D	0.779391457	None	None	N
L/Q	0.9926	likely_pathogenic	0.9967	pathogenic	-1.828	Destabilizing	0.998	D	0.904	deleterious	None	None	None	None	N
L/R	0.9927	likely_pathogenic	0.9959	pathogenic	-1.93	Destabilizing	0.997	D	0.889	deleterious	D	0.712311624	None	None	N
L/S	0.9965	likely_pathogenic	0.9985	pathogenic	-2.574	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
L/T	0.9898	likely_pathogenic	0.9949	pathogenic	-2.134	Highly Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
L/V	0.4215	ambiguous	0.5853	pathogenic	-0.991	Destabilizing	0.955	D	0.686	prob.neutral	D	0.632333419	None	None	N
L/W	0.9833	likely_pathogenic	0.9941	pathogenic	-1.559	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/Y	0.9831	likely_pathogenic	0.9926	pathogenic	-1.427	Destabilizing	0.998	D	0.845	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.