TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5726	17401;17402;17403	chr2:178731699;178731698;178731697	chr2:179596426;179596425;179596424
N2AB	5409	16450;16451;16452	chr2:178731699;178731698;178731697	chr2:179596426;179596425;179596424
N2A	4482	13669;13670;13671	chr2:178731699;178731698;178731697	chr2:179596426;179596425;179596424
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: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-40
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.7116
• 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/I	None	None	0.956	N	0.401	0.133	0.223847106136	gnomAD-4.0.0	1.60296E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03933E-05

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	0.462	ambiguous	0.3825	ambiguous	-1.617	Destabilizing	0.983	D	0.471	neutral	None	None	None	None	I
L/C	0.687	likely_pathogenic	0.6182	pathogenic	-0.892	Destabilizing	1.0	D	0.536	neutral	None	None	None	None	I
L/D	0.9378	likely_pathogenic	0.9114	pathogenic	-0.773	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	I
L/E	0.655	likely_pathogenic	0.5826	pathogenic	-0.698	Destabilizing	0.99	D	0.591	neutral	None	None	None	None	I
L/F	0.2373	likely_benign	0.2084	benign	-0.891	Destabilizing	0.994	D	0.457	neutral	N	0.505943861	None	None	I
L/G	0.7924	likely_pathogenic	0.7137	pathogenic	-2.008	Highly Destabilizing	0.998	D	0.643	neutral	None	None	None	None	I
L/H	0.5476	ambiguous	0.4773	ambiguous	-1.158	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	I
L/I	0.1132	likely_benign	0.1121	benign	-0.587	Destabilizing	0.956	D	0.401	neutral	N	0.456146972	None	None	I
L/K	0.5844	likely_pathogenic	0.507	ambiguous	-1.0	Destabilizing	0.99	D	0.501	neutral	None	None	None	None	I
L/M	0.1492	likely_benign	0.1381	benign	-0.495	Destabilizing	0.923	D	0.321	neutral	None	None	None	None	I
L/N	0.7476	likely_pathogenic	0.6726	pathogenic	-0.934	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	I
L/P	0.5688	likely_pathogenic	0.4511	ambiguous	-0.9	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
L/Q	0.3046	likely_benign	0.2519	benign	-0.986	Destabilizing	0.923	D	0.357	neutral	None	None	None	None	I
L/R	0.4544	ambiguous	0.3997	ambiguous	-0.558	Destabilizing	0.995	D	0.595	neutral	None	None	None	None	I
L/S	0.5832	likely_pathogenic	0.4866	ambiguous	-1.652	Destabilizing	0.994	D	0.501	neutral	N	0.47289777	None	None	I
L/T	0.4424	ambiguous	0.3785	ambiguous	-1.45	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	I
L/V	0.1111	likely_benign	0.1069	benign	-0.9	Destabilizing	0.956	D	0.417	neutral	N	0.390614547	None	None	I
L/W	0.4944	ambiguous	0.4316	ambiguous	-1.026	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	I
L/Y	0.6046	likely_pathogenic	0.5295	ambiguous	-0.765	Destabilizing	0.999	D	0.525	neutral	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.