TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20447	61564;61565;61566	chr2:178590386;178590385;178590384	chr2:179455113;179455112;179455111
N2AB	18806	56641;56642;56643	chr2:178590386;178590385;178590384	chr2:179455113;179455112;179455111
N2A	17879	53860;53861;53862	chr2:178590386;178590385;178590384	chr2:179455113;179455112;179455111
N2B	11382	34369;34370;34371	chr2:178590386;178590385;178590384	chr2:179455113;179455112;179455111
Novex-1	11507	34744;34745;34746	chr2:178590386;178590385;178590384	chr2:179455113;179455112;179455111
Novex-2	11574	34945;34946;34947	chr2:178590386;178590385;178590384	chr2:179455113;179455112;179455111
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-36
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0701
• 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/T	None	None	0.961	N	0.564	0.501	0.716551085193	gnomAD-4.0.0	6.92752E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05938E-07	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	0.9824	likely_pathogenic	0.98	pathogenic	-3.384	Highly Destabilizing	0.931	D	0.617	neutral	None	None	None	None	N
I/C	0.9687	likely_pathogenic	0.9694	pathogenic	-2.611	Highly Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9995	pathogenic	-4.05	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
I/E	0.9984	likely_pathogenic	0.9972	pathogenic	-3.768	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
I/F	0.8904	likely_pathogenic	0.8722	pathogenic	-2.078	Highly Destabilizing	0.996	D	0.626	neutral	None	None	None	None	N
I/G	0.9967	likely_pathogenic	0.9962	pathogenic	-3.913	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
I/H	0.999	likely_pathogenic	0.9984	pathogenic	-3.335	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
I/K	0.9973	likely_pathogenic	0.9956	pathogenic	-2.914	Highly Destabilizing	0.998	D	0.835	deleterious	N	0.508420804	None	None	N
I/L	0.5219	ambiguous	0.4978	ambiguous	-1.774	Destabilizing	0.689	D	0.283	neutral	N	0.513518486	None	None	N
I/M	0.6116	likely_pathogenic	0.5739	pathogenic	-1.848	Destabilizing	0.994	D	0.625	neutral	N	0.475984503	None	None	N
I/N	0.995	likely_pathogenic	0.9912	pathogenic	-3.515	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
I/P	0.998	likely_pathogenic	0.9977	pathogenic	-2.306	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9975	likely_pathogenic	0.9958	pathogenic	-3.269	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
I/R	0.9959	likely_pathogenic	0.9936	pathogenic	-2.602	Highly Destabilizing	0.998	D	0.869	deleterious	N	0.508420804	None	None	N
I/S	0.9919	likely_pathogenic	0.9886	pathogenic	-4.053	Highly Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
I/T	0.9851	likely_pathogenic	0.9783	pathogenic	-3.644	Highly Destabilizing	0.961	D	0.564	neutral	N	0.496811009	None	None	N
I/V	0.1289	likely_benign	0.1305	benign	-2.306	Highly Destabilizing	0.044	N	0.204	neutral	N	0.348360572	None	None	N
I/W	0.9977	likely_pathogenic	0.9972	pathogenic	-2.474	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
I/Y	0.9924	likely_pathogenic	0.9891	pathogenic	-2.378	Highly Destabilizing	0.999	D	0.709	prob.delet.	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.