TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24414	73465;73466;73467	chr2:178572892;178572891;178572890	chr2:179437619;179437618;179437617
N2AB	22773	68542;68543;68544	chr2:178572892;178572891;178572890	chr2:179437619;179437618;179437617
N2A	21846	65761;65762;65763	chr2:178572892;178572891;178572890	chr2:179437619;179437618;179437617
N2B	15349	46270;46271;46272	chr2:178572892;178572891;178572890	chr2:179437619;179437618;179437617
Novex-1	15474	46645;46646;46647	chr2:178572892;178572891;178572890	chr2:179437619;179437618;179437617
Novex-2	15541	46846;46847;46848	chr2:178572892;178572891;178572890	chr2:179437619;179437618;179437617
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-65
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.7562
• 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
P/R	rs769320646	None	0.987	N	0.634	0.46	0.527557778142	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
P/R	rs769320646	None	0.987	N	0.634	0.46	0.527557778142	gnomAD-4.0.0	2.05312E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69879E-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
P/A	0.1156	likely_benign	0.1083	benign	-0.441	Destabilizing	0.032	N	0.418	neutral	N	0.521815469	None	None	I
P/C	0.6137	likely_pathogenic	0.5783	pathogenic	-0.697	Destabilizing	0.997	D	0.666	prob.neutral	None	None	None	None	I
P/D	0.6368	likely_pathogenic	0.5609	ambiguous	-0.476	Destabilizing	0.99	D	0.709	prob.delet.	None	None	None	None	I
P/E	0.4447	ambiguous	0.3724	ambiguous	-0.577	Destabilizing	0.98	D	0.727	deleterious	None	None	None	None	I
P/F	0.6472	likely_pathogenic	0.604	pathogenic	-0.675	Destabilizing	0.997	D	0.642	neutral	None	None	None	None	I
P/G	0.419	ambiguous	0.3806	ambiguous	-0.558	Destabilizing	0.875	D	0.659	prob.neutral	None	None	None	None	I
P/H	0.3159	likely_benign	0.2817	benign	-0.13	Destabilizing	0.999	D	0.638	neutral	N	0.488585483	None	None	I
P/I	0.4301	ambiguous	0.4021	ambiguous	-0.273	Destabilizing	0.98	D	0.653	prob.neutral	None	None	None	None	I
P/K	0.5057	ambiguous	0.4253	ambiguous	-0.526	Destabilizing	0.98	D	0.732	deleterious	None	None	None	None	I
P/L	0.1706	likely_benign	0.1608	benign	-0.273	Destabilizing	0.949	D	0.627	neutral	N	0.488496578	None	None	I
P/M	0.3873	ambiguous	0.3633	ambiguous	-0.519	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
P/N	0.4556	ambiguous	0.4228	ambiguous	-0.305	Destabilizing	0.99	D	0.647	neutral	None	None	None	None	I
P/Q	0.2591	likely_benign	0.2237	benign	-0.516	Destabilizing	0.99	D	0.675	prob.neutral	None	None	None	None	I
P/R	0.376	ambiguous	0.3139	benign	-0.043	Destabilizing	0.987	D	0.634	neutral	N	0.510613304	None	None	I
P/S	0.1822	likely_benign	0.167	benign	-0.603	Destabilizing	0.949	D	0.738	deleterious	N	0.490319126	None	None	I
P/T	0.1418	likely_benign	0.1302	benign	-0.607	Destabilizing	0.974	D	0.689	prob.delet.	N	0.50305635	None	None	I
P/V	0.2929	likely_benign	0.2729	benign	-0.297	Destabilizing	0.961	D	0.607	neutral	None	None	None	None	I
P/W	0.7955	likely_pathogenic	0.7526	pathogenic	-0.771	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
P/Y	0.6246	likely_pathogenic	0.5864	pathogenic	-0.481	Destabilizing	0.999	D	0.636	neutral	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.