TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5056	15391;15392;15393	chr2:178734758;178734757;178734756	chr2:179599485;179599484;179599483
N2AB	4739	14440;14441;14442	chr2:178734758;178734757;178734756	chr2:179599485;179599484;179599483
N2A	3812	11659;11660;11661	chr2:178734758;178734757;178734756	chr2:179599485;179599484;179599483
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-33
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.089
• 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
A/S	rs763353350	None	0.946	D	0.663	0.583	0.498259528926	gnomAD-4.0.0	2.73751E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59859E-06	0	0
A/T	rs763353350	-1.532	0.896	D	0.662	0.604	0.524843318063	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
A/T	rs763353350	-1.532	0.896	D	0.662	0.604	0.524843318063	gnomAD-4.0.0	6.84377E-07	None	None	None	None	N	None	0	0	None	0	2.52029E-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
A/C	0.9268	likely_pathogenic	0.9148	pathogenic	-1.8	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
A/D	0.9953	likely_pathogenic	0.9954	pathogenic	-2.328	Highly Destabilizing	0.996	D	0.856	deleterious	None	None	None	None	N
A/E	0.9901	likely_pathogenic	0.9905	pathogenic	-2.197	Highly Destabilizing	0.984	D	0.832	deleterious	D	0.822504561	None	None	N
A/F	0.9495	likely_pathogenic	0.9423	pathogenic	-1.045	Destabilizing	0.976	D	0.853	deleterious	None	None	None	None	N
A/G	0.3918	ambiguous	0.418	ambiguous	-1.832	Destabilizing	0.946	D	0.659	neutral	D	0.674029768	None	None	N
A/H	0.9973	likely_pathogenic	0.9971	pathogenic	-1.933	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
A/I	0.6281	likely_pathogenic	0.6328	pathogenic	-0.302	Destabilizing	0.851	D	0.73	prob.delet.	None	None	None	None	N
A/K	0.9982	likely_pathogenic	0.998	pathogenic	-1.563	Destabilizing	0.988	D	0.827	deleterious	None	None	None	None	N
A/L	0.6655	likely_pathogenic	0.6239	pathogenic	-0.302	Destabilizing	0.702	D	0.724	prob.delet.	None	None	None	None	N
A/M	0.7679	likely_pathogenic	0.7699	pathogenic	-0.616	Destabilizing	0.988	D	0.818	deleterious	None	None	None	None	N
A/N	0.9899	likely_pathogenic	0.9895	pathogenic	-1.718	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
A/P	0.9908	likely_pathogenic	0.9909	pathogenic	-0.627	Destabilizing	0.995	D	0.834	deleterious	D	0.788246233	None	None	N
A/Q	0.9908	likely_pathogenic	0.9907	pathogenic	-1.668	Destabilizing	0.996	D	0.821	deleterious	None	None	None	None	N
A/R	0.9937	likely_pathogenic	0.9931	pathogenic	-1.429	Destabilizing	0.988	D	0.833	deleterious	None	None	None	None	N
A/S	0.5294	ambiguous	0.5473	ambiguous	-2.201	Highly Destabilizing	0.946	D	0.663	neutral	D	0.714580571	None	None	N
A/T	0.5973	likely_pathogenic	0.6262	pathogenic	-1.945	Destabilizing	0.896	D	0.662	neutral	D	0.72326977	None	None	N
A/V	0.3155	likely_benign	0.3267	benign	-0.627	Destabilizing	0.011	N	0.32	neutral	D	0.529070907	None	None	N
A/W	0.9976	likely_pathogenic	0.9972	pathogenic	-1.576	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
A/Y	0.9887	likely_pathogenic	0.9874	pathogenic	-1.125	Destabilizing	0.988	D	0.848	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.