TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2359	7300;7301;7302	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818
N2AB	2359	7300;7301;7302	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818
N2A	2359	7300;7301;7302	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818
N2B	2313	7162;7163;7164	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818
Novex-1	2313	7162;7163;7164	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818
Novex-2	2313	7162;7163;7164	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818
Novex-3	2359	7300;7301;7302	chr2:178774093;178774092;178774091	chr2:179638820;179638819;179638818

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-13
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4713
• 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/P	None	None	0.999	D	0.626	0.871	0.911129948677	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	1.26695E-04	0	None	0	0	None	0	0	0	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	0.4317	ambiguous	0.4154	ambiguous	-0.967	Destabilizing	0.983	D	0.391	neutral	None	None	None	None	I
L/C	0.6571	likely_pathogenic	0.6526	pathogenic	-0.755	Destabilizing	1.0	D	0.455	neutral	None	None	None	None	I
L/D	0.8843	likely_pathogenic	0.8671	pathogenic	-0.412	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
L/E	0.5462	ambiguous	0.4887	ambiguous	-0.475	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
L/F	0.1485	likely_benign	0.1446	benign	-0.732	Destabilizing	0.995	D	0.401	neutral	None	None	None	None	I
L/G	0.7534	likely_pathogenic	0.7312	pathogenic	-1.184	Destabilizing	0.998	D	0.626	neutral	None	None	None	None	I
L/H	0.3311	likely_benign	0.3108	benign	-0.318	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
L/I	0.0877	likely_benign	0.0907	benign	-0.493	Destabilizing	0.956	D	0.358	neutral	D	0.531571177	None	None	I
L/K	0.4812	ambiguous	0.4297	ambiguous	-0.651	Destabilizing	0.998	D	0.506	neutral	None	None	None	None	I
L/M	0.1135	likely_benign	0.1142	benign	-0.477	Destabilizing	0.693	D	0.162	neutral	None	None	None	None	I
L/N	0.5663	likely_pathogenic	0.5559	ambiguous	-0.488	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
L/P	0.8618	likely_pathogenic	0.8592	pathogenic	-0.617	Destabilizing	0.999	D	0.626	neutral	D	0.593097117	None	None	I
L/Q	0.2078	likely_benign	0.1829	benign	-0.708	Destabilizing	0.997	D	0.548	neutral	D	0.593097117	None	None	I
L/R	0.3863	ambiguous	0.3252	benign	-0.019	Destabilizing	0.997	D	0.561	neutral	D	0.542289307	None	None	I
L/S	0.4326	ambiguous	0.4079	ambiguous	-0.999	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	I
L/T	0.2769	likely_benign	0.2682	benign	-0.953	Destabilizing	0.998	D	0.415	neutral	None	None	None	None	I
L/V	0.1005	likely_benign	0.1013	benign	-0.617	Destabilizing	0.9	D	0.415	neutral	N	0.497581761	None	None	I
L/W	0.3805	ambiguous	0.3501	ambiguous	-0.739	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	I
L/Y	0.445	ambiguous	0.4309	ambiguous	-0.521	Destabilizing	0.999	D	0.424	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.