TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31747	95464;95465;95466	chr2:178545997;178545996;178545995	chr2:179410724;179410723;179410722
N2AB	30106	90541;90542;90543	chr2:178545997;178545996;178545995	chr2:179410724;179410723;179410722
N2A	29179	87760;87761;87762	chr2:178545997;178545996;178545995	chr2:179410724;179410723;179410722
N2B	22682	68269;68270;68271	chr2:178545997;178545996;178545995	chr2:179410724;179410723;179410722
Novex-1	22807	68644;68645;68646	chr2:178545997;178545996;178545995	chr2:179410724;179410723;179410722
Novex-2	22874	68845;68846;68847	chr2:178545997;178545996;178545995	chr2:179410724;179410723;179410722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-119
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1859
• 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
R/I	None	None	1.0	N	0.885	0.446	0.627195870872	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
R/A	0.9576	likely_pathogenic	0.9688	pathogenic	-2.063	Highly Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
R/C	0.5902	likely_pathogenic	0.621	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
R/D	0.9927	likely_pathogenic	0.9936	pathogenic	-1.317	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
R/E	0.9264	likely_pathogenic	0.9371	pathogenic	-1.064	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
R/F	0.9562	likely_pathogenic	0.9601	pathogenic	-1.168	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
R/G	0.9128	likely_pathogenic	0.9316	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.833	deleterious	N	0.473913225	None	None	I
R/H	0.4477	ambiguous	0.4704	ambiguous	-1.739	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
R/I	0.861	likely_pathogenic	0.8821	pathogenic	-0.956	Destabilizing	1.0	D	0.885	deleterious	N	0.519460237	None	None	I
R/K	0.2236	likely_benign	0.2178	benign	-1.114	Destabilizing	0.997	D	0.651	neutral	N	0.388359834	None	None	I
R/L	0.8078	likely_pathogenic	0.8385	pathogenic	-0.956	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
R/M	0.8338	likely_pathogenic	0.8606	pathogenic	-1.442	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
R/N	0.9793	likely_pathogenic	0.9814	pathogenic	-1.67	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
R/P	0.9974	likely_pathogenic	0.9977	pathogenic	-1.316	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
R/Q	0.3731	ambiguous	0.4197	ambiguous	-1.493	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
R/S	0.9723	likely_pathogenic	0.9764	pathogenic	-2.562	Highly Destabilizing	1.0	D	0.826	deleterious	N	0.469949979	None	None	I
R/T	0.9272	likely_pathogenic	0.9424	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.825	deleterious	N	0.477178455	None	None	I
R/V	0.9031	likely_pathogenic	0.9179	pathogenic	-1.316	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
R/W	0.6684	likely_pathogenic	0.6834	pathogenic	-0.614	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
R/Y	0.8416	likely_pathogenic	0.8381	pathogenic	-0.556	Destabilizing	1.0	D	0.889	deleterious	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.