TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1783	5572;5573;5574	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242
N2AB	1783	5572;5573;5574	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242
N2A	1783	5572;5573;5574	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242
N2B	1737	5434;5435;5436	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242
Novex-1	1737	5434;5435;5436	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242
Novex-2	1737	5434;5435;5436	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242
Novex-3	1783	5572;5573;5574	chr2:178776517;178776516;178776515	chr2:179641244;179641243;179641242

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-8
• Domain position: 81
• Structural Position: 163
• Q(SASA): 0.8144
• 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
Y/C	None	None	1.0	N	0.641	0.426	0.52891208781	gnomAD-4.0.0	1.60245E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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
Y/A	0.9375	likely_pathogenic	0.9285	pathogenic	-0.434	Destabilizing	0.992	D	0.549	neutral	None	None	None	None	I
Y/C	0.7865	likely_pathogenic	0.7392	pathogenic	0.114	Stabilizing	1.0	D	0.641	neutral	N	0.500497634	None	None	I
Y/D	0.9124	likely_pathogenic	0.8945	pathogenic	0.678	Stabilizing	0.999	D	0.621	neutral	D	0.541492705	None	None	I
Y/E	0.9768	likely_pathogenic	0.971	pathogenic	0.647	Stabilizing	0.999	D	0.608	neutral	None	None	None	None	I
Y/F	0.1413	likely_benign	0.1443	benign	-0.297	Destabilizing	0.121	N	0.354	neutral	N	0.486900949	None	None	I
Y/G	0.9311	likely_pathogenic	0.9173	pathogenic	-0.584	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	I
Y/H	0.6177	likely_pathogenic	0.5848	pathogenic	0.339	Stabilizing	0.999	D	0.586	neutral	N	0.459933374	None	None	I
Y/I	0.9417	likely_pathogenic	0.9275	pathogenic	-0.076	Destabilizing	0.995	D	0.565	neutral	None	None	None	None	I
Y/K	0.9789	likely_pathogenic	0.9714	pathogenic	0.23	Stabilizing	0.999	D	0.603	neutral	None	None	None	None	I
Y/L	0.8917	likely_pathogenic	0.8785	pathogenic	-0.076	Destabilizing	0.967	D	0.595	neutral	None	None	None	None	I
Y/M	0.9466	likely_pathogenic	0.9273	pathogenic	-0.1	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	I
Y/N	0.6606	likely_pathogenic	0.6185	pathogenic	-0.031	Destabilizing	0.999	D	0.612	neutral	N	0.511387921	None	None	I
Y/P	0.9962	likely_pathogenic	0.9958	pathogenic	-0.176	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
Y/Q	0.959	likely_pathogenic	0.9478	pathogenic	0.029	Stabilizing	0.999	D	0.6	neutral	None	None	None	None	I
Y/R	0.9544	likely_pathogenic	0.9393	pathogenic	0.417	Stabilizing	0.999	D	0.612	neutral	None	None	None	None	I
Y/S	0.8493	likely_pathogenic	0.831	pathogenic	-0.344	Destabilizing	0.999	D	0.595	neutral	N	0.503482246	None	None	I
Y/T	0.9594	likely_pathogenic	0.9441	pathogenic	-0.287	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	I
Y/V	0.8893	likely_pathogenic	0.8697	pathogenic	-0.176	Destabilizing	0.983	D	0.584	neutral	None	None	None	None	I
Y/W	0.7198	likely_pathogenic	0.6933	pathogenic	-0.52	Destabilizing	1.0	D	0.589	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.