TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9390	28393;28394;28395	chr2:178711068;178711067;178711066	chr2:179575795;179575794;179575793
N2AB	9073	27442;27443;27444	chr2:178711068;178711067;178711066	chr2:179575795;179575794;179575793
N2A	8146	24661;24662;24663	chr2:178711068;178711067;178711066	chr2:179575795;179575794;179575793
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-79
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4213
• 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	0.981	None	0.479	0.248	0.414798848334	gnomAD-4.0.0	1.68155E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.57085E-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	0.6465	likely_pathogenic	0.6577	pathogenic	-1.963	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	I
L/C	0.8283	likely_pathogenic	0.8474	pathogenic	-1.204	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
L/D	0.9886	likely_pathogenic	0.9936	pathogenic	-1.555	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
L/E	0.9296	likely_pathogenic	0.9547	pathogenic	-1.508	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
L/F	0.5068	ambiguous	0.5572	ambiguous	-1.333	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	I
L/G	0.9206	likely_pathogenic	0.936	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
L/H	0.8879	likely_pathogenic	0.9209	pathogenic	-1.606	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
L/I	0.1104	likely_benign	0.129	benign	-0.965	Destabilizing	0.981	D	0.479	neutral	None	None	None	None	I
L/K	0.9143	likely_pathogenic	0.9498	pathogenic	-1.33	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
L/M	0.2612	likely_benign	0.2767	benign	-0.771	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
L/N	0.919	likely_pathogenic	0.9416	pathogenic	-1.197	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
L/P	0.8309	likely_pathogenic	0.8969	pathogenic	-1.269	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
L/Q	0.7768	likely_pathogenic	0.8387	pathogenic	-1.339	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
L/R	0.8402	likely_pathogenic	0.9005	pathogenic	-0.79	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
L/S	0.8519	likely_pathogenic	0.8734	pathogenic	-1.856	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
L/T	0.5925	likely_pathogenic	0.6375	pathogenic	-1.691	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	I
L/V	0.116	likely_benign	0.1382	benign	-1.269	Destabilizing	0.767	D	0.224	neutral	None	None	None	None	I
L/W	0.8744	likely_pathogenic	0.9211	pathogenic	-1.468	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
L/Y	0.901	likely_pathogenic	0.9261	pathogenic	-1.233	Destabilizing	1.0	D	0.701	prob.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.