TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33726	101401;101402;101403	chr2:178535439;178535438;178535437	chr2:179400166;179400165;179400164
N2AB	32085	96478;96479;96480	chr2:178535439;178535438;178535437	chr2:179400166;179400165;179400164
N2A	31158	93697;93698;93699	chr2:178535439;178535438;178535437	chr2:179400166;179400165;179400164
N2B	24661	74206;74207;74208	chr2:178535439;178535438;178535437	chr2:179400166;179400165;179400164
Novex-1	24786	74581;74582;74583	chr2:178535439;178535438;178535437	chr2:179400166;179400165;179400164
Novex-2	24853	74782;74783;74784	chr2:178535439;178535438;178535437	chr2:179400166;179400165;179400164
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-132
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.101
• 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
V/A	None	None	0.23	D	0.579	0.575	0.680060995016	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	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
V/A	0.9083	likely_pathogenic	0.8906	pathogenic	-2.524	Highly Destabilizing	0.23	N	0.579	neutral	D	0.539666834	None	None	N
V/C	0.9742	likely_pathogenic	0.976	pathogenic	-1.725	Destabilizing	0.987	D	0.79	deleterious	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9981	pathogenic	-3.445	Highly Destabilizing	0.997	D	0.876	deleterious	D	0.540427303	None	None	N
V/E	0.9947	likely_pathogenic	0.993	pathogenic	-3.12	Highly Destabilizing	0.988	D	0.815	deleterious	None	None	None	None	N
V/F	0.8324	likely_pathogenic	0.8138	pathogenic	-1.462	Destabilizing	0.825	D	0.725	prob.delet.	D	0.540173813	None	None	N
V/G	0.9762	likely_pathogenic	0.9678	pathogenic	-3.119	Highly Destabilizing	0.945	D	0.839	deleterious	D	0.540427303	None	None	N
V/H	0.9983	likely_pathogenic	0.9981	pathogenic	-2.961	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.0686	likely_benign	0.0706	benign	-0.773	Destabilizing	None	N	0.183	neutral	N	0.43459913	None	None	N
V/K	0.9956	likely_pathogenic	0.9941	pathogenic	-2.079	Highly Destabilizing	0.995	D	0.818	deleterious	None	None	None	None	N
V/L	0.4355	ambiguous	0.3953	ambiguous	-0.773	Destabilizing	None	N	0.323	neutral	N	0.471890868	None	None	N
V/M	0.6556	likely_pathogenic	0.6422	pathogenic	-0.962	Destabilizing	0.817	D	0.633	neutral	None	None	None	None	N
V/N	0.9944	likely_pathogenic	0.9942	pathogenic	-2.801	Highly Destabilizing	0.988	D	0.877	deleterious	None	None	None	None	N
V/P	0.9908	likely_pathogenic	0.9918	pathogenic	-1.342	Destabilizing	0.988	D	0.854	deleterious	None	None	None	None	N
V/Q	0.9941	likely_pathogenic	0.9926	pathogenic	-2.426	Highly Destabilizing	0.997	D	0.871	deleterious	None	None	None	None	N
V/R	0.9911	likely_pathogenic	0.9883	pathogenic	-2.171	Highly Destabilizing	0.997	D	0.876	deleterious	None	None	None	None	N
V/S	0.9805	likely_pathogenic	0.9776	pathogenic	-3.262	Highly Destabilizing	0.995	D	0.766	deleterious	None	None	None	None	N
V/T	0.9114	likely_pathogenic	0.8955	pathogenic	-2.783	Highly Destabilizing	0.923	D	0.59	neutral	None	None	None	None	N
V/W	0.9969	likely_pathogenic	0.9962	pathogenic	-1.991	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9917	likely_pathogenic	0.99	pathogenic	-1.72	Destabilizing	0.997	D	0.759	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.