TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22821	68686;68687;68688	chr2:178578054;178578053;178578052	chr2:179442781;179442780;179442779
N2AB	21180	63763;63764;63765	chr2:178578054;178578053;178578052	chr2:179442781;179442780;179442779
N2A	20253	60982;60983;60984	chr2:178578054;178578053;178578052	chr2:179442781;179442780;179442779
N2B	13756	41491;41492;41493	chr2:178578054;178578053;178578052	chr2:179442781;179442780;179442779
Novex-1	13881	41866;41867;41868	chr2:178578054;178578053;178578052	chr2:179442781;179442780;179442779
Novex-2	13948	42067;42068;42069	chr2:178578054;178578053;178578052	chr2:179442781;179442780;179442779
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: Fn3-53
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1591
• 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/N	rs773379003	-1.657	0.999	N	0.731	0.543	0.786870034503	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	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	0.5742	likely_pathogenic	0.5713	pathogenic	-2.452	Highly Destabilizing	0.985	D	0.566	neutral	None	None	None	None	N
I/C	0.7804	likely_pathogenic	0.7773	pathogenic	-1.817	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
I/D	0.9415	likely_pathogenic	0.9554	pathogenic	-2.947	Highly Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
I/E	0.7137	likely_pathogenic	0.7282	pathogenic	-2.794	Highly Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
I/F	0.3596	ambiguous	0.3601	ambiguous	-1.512	Destabilizing	0.994	D	0.565	neutral	N	0.466071256	None	None	N
I/G	0.8769	likely_pathogenic	0.8852	pathogenic	-2.921	Highly Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
I/H	0.8457	likely_pathogenic	0.8635	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
I/K	0.7372	likely_pathogenic	0.7834	pathogenic	-1.811	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
I/L	0.15	likely_benign	0.1303	benign	-1.122	Destabilizing	0.061	N	0.209	neutral	N	0.427800869	None	None	N
I/M	0.1084	likely_benign	0.1048	benign	-1.075	Destabilizing	0.659	D	0.395	neutral	N	0.44800557	None	None	N
I/N	0.6823	likely_pathogenic	0.7071	pathogenic	-2.015	Highly Destabilizing	0.999	D	0.731	prob.delet.	N	0.473229302	None	None	N
I/P	0.9924	likely_pathogenic	0.9934	pathogenic	-1.545	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
I/Q	0.6418	likely_pathogenic	0.661	pathogenic	-1.997	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
I/R	0.6874	likely_pathogenic	0.7384	pathogenic	-1.405	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
I/S	0.5968	likely_pathogenic	0.6111	pathogenic	-2.633	Highly Destabilizing	0.997	D	0.623	neutral	N	0.464359102	None	None	N
I/T	0.4609	ambiguous	0.4861	ambiguous	-2.355	Highly Destabilizing	0.99	D	0.571	neutral	N	0.438327294	None	None	N
I/V	0.0793	likely_benign	0.0792	benign	-1.545	Destabilizing	0.817	D	0.381	neutral	N	0.364591966	None	None	N
I/W	0.9168	likely_pathogenic	0.9353	pathogenic	-1.901	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
I/Y	0.7927	likely_pathogenic	0.8076	pathogenic	-1.649	Destabilizing	0.999	D	0.63	neutral	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.