TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15503	46732;46733;46734	chr2:178619810;178619809;178619808	chr2:179484537;179484536;179484535
N2AB	13862	41809;41810;41811	chr2:178619810;178619809;178619808	chr2:179484537;179484536;179484535
N2A	12935	39028;39029;39030	chr2:178619810;178619809;178619808	chr2:179484537;179484536;179484535
N2B	6438	19537;19538;19539	chr2:178619810;178619809;178619808	chr2:179484537;179484536;179484535
Novex-1	6563	19912;19913;19914	chr2:178619810;178619809;178619808	chr2:179484537;179484536;179484535
Novex-2	6630	20113;20114;20115	chr2:178619810;178619809;178619808	chr2:179484537;179484536;179484535
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-107
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1156
• 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/V	None	None	0.999	N	0.53	0.215	0.326881540566	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9418	likely_pathogenic	0.9388	pathogenic	-2.998	Highly Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
L/C	0.8999	likely_pathogenic	0.9209	pathogenic	-2.316	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.618	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/E	0.9955	likely_pathogenic	0.9956	pathogenic	-3.372	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/F	0.9104	likely_pathogenic	0.9232	pathogenic	-1.663	Destabilizing	1.0	D	0.789	deleterious	N	0.512350285	None	None	N
L/G	0.987	likely_pathogenic	0.9891	pathogenic	-3.534	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9942	likely_pathogenic	0.9942	pathogenic	-2.935	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.555963575	None	None	N
L/I	0.3442	ambiguous	0.3117	benign	-1.406	Destabilizing	0.999	D	0.529	neutral	N	0.484652081	None	None	N
L/K	0.9926	likely_pathogenic	0.9934	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/M	0.4792	ambiguous	0.495	ambiguous	-1.499	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/N	0.9948	likely_pathogenic	0.9942	pathogenic	-2.789	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/P	0.9959	likely_pathogenic	0.9972	pathogenic	-1.925	Destabilizing	1.0	D	0.845	deleterious	D	0.555963575	None	None	N
L/Q	0.9911	likely_pathogenic	0.9895	pathogenic	-2.605	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/R	0.987	likely_pathogenic	0.9887	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.555963575	None	None	N
L/S	0.9935	likely_pathogenic	0.9928	pathogenic	-3.408	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/T	0.9221	likely_pathogenic	0.9103	pathogenic	-3.031	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/V	0.3092	likely_benign	0.2378	benign	-1.925	Destabilizing	0.999	D	0.53	neutral	N	0.459898247	None	None	N
L/W	0.9915	likely_pathogenic	0.9932	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/Y	0.9909	likely_pathogenic	0.9916	pathogenic	-1.945	Destabilizing	1.0	D	0.839	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.