TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1326	4201;4202;4203	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831
N2AB	1326	4201;4202;4203	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831
N2A	1326	4201;4202;4203	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831
N2B	1280	4063;4064;4065	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831
Novex-1	1280	4063;4064;4065	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831
Novex-2	1280	4063;4064;4065	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831
Novex-3	1326	4201;4202;4203	chr2:178779106;178779105;178779104	chr2:179643833;179643832;179643831

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-5
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1313
• 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
K/E	rs2092529339	None	0.999	D	0.615	0.529	0.479593739615	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
K/E	rs2092529339	None	0.999	D	0.615	0.529	0.479593739615	gnomAD-4.0.0	2.02974E-06	None	None	None	None	N	None	0	6.14855E-05	None	0	0	None	0	0	1.20489E-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
K/A	0.9928	likely_pathogenic	0.9933	pathogenic	-1.195	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
K/C	0.9799	likely_pathogenic	0.9839	pathogenic	-1.252	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
K/D	0.9996	likely_pathogenic	0.9996	pathogenic	-0.845	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/E	0.9926	likely_pathogenic	0.9937	pathogenic	-0.626	Destabilizing	0.999	D	0.615	neutral	D	0.717145636	None	None	N
K/F	0.9981	likely_pathogenic	0.9983	pathogenic	-0.742	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
K/G	0.9978	likely_pathogenic	0.9979	pathogenic	-1.645	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/H	0.9264	likely_pathogenic	0.9365	pathogenic	-1.897	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/I	0.9834	likely_pathogenic	0.9864	pathogenic	0.034	Stabilizing	1.0	D	0.877	deleterious	D	0.599276767	None	None	N
K/L	0.9729	likely_pathogenic	0.9775	pathogenic	0.034	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/M	0.9672	likely_pathogenic	0.9715	pathogenic	-0.118	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/N	0.9977	likely_pathogenic	0.998	pathogenic	-1.209	Destabilizing	1.0	D	0.753	deleterious	D	0.595311666	None	None	N
K/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.349	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/Q	0.9266	likely_pathogenic	0.9377	pathogenic	-1.077	Destabilizing	1.0	D	0.741	deleterious	D	0.594464314	None	None	N
K/R	0.2547	likely_benign	0.2792	benign	-0.885	Destabilizing	0.999	D	0.641	neutral	N	0.461271391	None	None	N
K/S	0.9975	likely_pathogenic	0.9976	pathogenic	-1.923	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
K/T	0.9908	likely_pathogenic	0.9907	pathogenic	-1.447	Destabilizing	1.0	D	0.792	deleterious	D	0.6276967	None	None	N
K/V	0.9691	likely_pathogenic	0.9724	pathogenic	-0.349	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/W	0.9971	likely_pathogenic	0.9976	pathogenic	-0.642	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
K/Y	0.9912	likely_pathogenic	0.9926	pathogenic	-0.306	Destabilizing	1.0	D	0.861	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.