TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26418	79477;79478;79479	chr2:178566880;178566879;178566878	chr2:179431607;179431606;179431605
N2AB	24777	74554;74555;74556	chr2:178566880;178566879;178566878	chr2:179431607;179431606;179431605
N2A	23850	71773;71774;71775	chr2:178566880;178566879;178566878	chr2:179431607;179431606;179431605
N2B	17353	52282;52283;52284	chr2:178566880;178566879;178566878	chr2:179431607;179431606;179431605
Novex-1	17478	52657;52658;52659	chr2:178566880;178566879;178566878	chr2:179431607;179431606;179431605
Novex-2	17545	52858;52859;52860	chr2:178566880;178566879;178566878	chr2:179431607;179431606;179431605
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-80
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2155
• 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
I/V	rs1382272786	-1.613	0.993	N	0.387	0.269	0.599423059063	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
I/V	rs1382272786	-1.613	0.993	N	0.387	0.269	0.599423059063	gnomAD-4.0.0	1.3686E-06	None	None	None	None	I	None	0	0	None	0	5.04414E-05	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	0.9861	likely_pathogenic	0.9871	pathogenic	-2.452	Highly Destabilizing	0.999	D	0.67	neutral	None	None	None	None	I
I/C	0.9877	likely_pathogenic	0.9894	pathogenic	-1.564	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
I/D	0.9989	likely_pathogenic	0.9987	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
I/E	0.9974	likely_pathogenic	0.9971	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
I/F	0.9494	likely_pathogenic	0.954	pathogenic	-1.579	Destabilizing	1.0	D	0.826	deleterious	D	0.542476494	None	None	I
I/G	0.9975	likely_pathogenic	0.9975	pathogenic	-2.916	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
I/H	0.9984	likely_pathogenic	0.9984	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
I/K	0.9964	likely_pathogenic	0.9959	pathogenic	-1.807	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
I/L	0.5477	ambiguous	0.5968	pathogenic	-1.153	Destabilizing	0.993	D	0.405	neutral	N	0.485846324	None	None	I
I/M	0.6096	likely_pathogenic	0.628	pathogenic	-0.9	Destabilizing	1.0	D	0.807	deleterious	D	0.545011389	None	None	I
I/N	0.9749	likely_pathogenic	0.9734	pathogenic	-1.879	Destabilizing	1.0	D	0.871	deleterious	D	0.552773297	None	None	I
I/P	0.9872	likely_pathogenic	0.9838	pathogenic	-1.563	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
I/Q	0.9972	likely_pathogenic	0.9973	pathogenic	-1.91	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
I/R	0.9956	likely_pathogenic	0.995	pathogenic	-1.3	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
I/S	0.99	likely_pathogenic	0.9909	pathogenic	-2.556	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.552012828	None	None	I
I/T	0.9791	likely_pathogenic	0.9816	pathogenic	-2.299	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.527160623	None	None	I
I/V	0.1598	likely_benign	0.1901	benign	-1.563	Destabilizing	0.993	D	0.387	neutral	N	0.520639246	None	None	I
I/W	0.9985	likely_pathogenic	0.9984	pathogenic	-1.875	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
I/Y	0.9926	likely_pathogenic	0.9924	pathogenic	-1.632	Destabilizing	1.0	D	0.861	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.