TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6135	18628;18629;18630	chr2:178729850;178729849;178729848	chr2:179594577;179594576;179594575
N2AB	5818	17677;17678;17679	chr2:178729850;178729849;178729848	chr2:179594577;179594576;179594575
N2A	4891	14896;14897;14898	chr2:178729850;178729849;178729848	chr2:179594577;179594576;179594575
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-45
• Domain position: 31
• Structural Position: 44
• Q(SASA): 0.1645
• 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
I/V	rs935669018	None	0.993	D	0.38	0.287	0.580574400314	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.31182E-04	0	0	0	None	0	0	0	0	0
I/V	rs935669018	None	0.993	D	0.38	0.287	0.580574400314	gnomAD-4.0.0	3.84409E-06	None	None	None	None	N	None	1.69159E-05	3.39271E-05	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
I/A	0.7469	likely_pathogenic	0.7396	pathogenic	-2.21	Highly Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
I/C	0.922	likely_pathogenic	0.9149	pathogenic	-1.466	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
I/D	0.947	likely_pathogenic	0.9441	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
I/E	0.9118	likely_pathogenic	0.9018	pathogenic	-1.919	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
I/F	0.4022	ambiguous	0.4616	ambiguous	-1.317	Destabilizing	1.0	D	0.781	deleterious	N	0.494847043	None	None	N
I/G	0.9117	likely_pathogenic	0.9061	pathogenic	-2.704	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/H	0.9183	likely_pathogenic	0.9192	pathogenic	-2.108	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
I/K	0.8709	likely_pathogenic	0.8589	pathogenic	-1.636	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
I/L	0.2096	likely_benign	0.2252	benign	-0.827	Destabilizing	0.993	D	0.409	neutral	N	0.509139748	None	None	N
I/M	0.1645	likely_benign	0.1875	benign	-0.739	Destabilizing	1.0	D	0.757	deleterious	D	0.532827471	None	None	N
I/N	0.6072	likely_pathogenic	0.5968	pathogenic	-1.771	Destabilizing	1.0	D	0.835	deleterious	N	0.521852068	None	None	N
I/P	0.6024	likely_pathogenic	0.5908	pathogenic	-1.264	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
I/Q	0.8821	likely_pathogenic	0.8808	pathogenic	-1.719	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
I/R	0.8404	likely_pathogenic	0.8312	pathogenic	-1.292	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/S	0.7179	likely_pathogenic	0.72	pathogenic	-2.483	Highly Destabilizing	1.0	D	0.812	deleterious	N	0.494847043	None	None	N
I/T	0.7384	likely_pathogenic	0.7144	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.773	deleterious	N	0.509824199	None	None	N
I/V	0.1749	likely_benign	0.1567	benign	-1.264	Destabilizing	0.993	D	0.38	neutral	D	0.534558267	None	None	N
I/W	0.9536	likely_pathogenic	0.9557	pathogenic	-1.628	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
I/Y	0.7963	likely_pathogenic	0.8152	pathogenic	-1.331	Destabilizing	1.0	D	0.814	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.