TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7570	22933;22934;22935	chr2:178721955;178721954;178721953	chr2:179586682;179586681;179586680
N2AB	7253	21982;21983;21984	chr2:178721955;178721954;178721953	chr2:179586682;179586681;179586680
N2A	6326	19201;19202;19203	chr2:178721955;178721954;178721953	chr2:179586682;179586681;179586680
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-60
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1114
• 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
P/A	None	None	0.011	N	0.53	0.163	0.0666544352282	gnomAD-4.0.0	6.84332E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73671E-04	0	0	0
P/H	rs1444461312	-2.167	0.999	N	0.783	0.418	0.297031009988	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/H	rs1444461312	-2.167	0.999	N	0.783	0.418	0.297031009988	gnomAD-4.0.0	1.59191E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	0
P/T	None	None	0.811	N	0.763	0.181	0.200317383148	gnomAD-4.0.0	6.84332E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99627E-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
P/A	0.0832	likely_benign	0.0879	benign	-1.873	Destabilizing	0.011	N	0.53	neutral	N	0.299092119	None	None	N
P/C	0.5709	likely_pathogenic	0.5687	pathogenic	-1.635	Destabilizing	0.997	D	0.808	deleterious	None	None	None	None	N
P/D	0.9365	likely_pathogenic	0.9346	pathogenic	-3.087	Highly Destabilizing	0.919	D	0.769	deleterious	None	None	None	None	N
P/E	0.8369	likely_pathogenic	0.841	pathogenic	-2.902	Highly Destabilizing	0.919	D	0.763	deleterious	None	None	None	None	N
P/F	0.7224	likely_pathogenic	0.7378	pathogenic	-1.042	Destabilizing	0.988	D	0.822	deleterious	None	None	None	None	N
P/G	0.5379	ambiguous	0.5164	ambiguous	-2.355	Highly Destabilizing	0.851	D	0.739	prob.delet.	None	None	None	None	N
P/H	0.5331	ambiguous	0.5381	ambiguous	-2.344	Highly Destabilizing	0.999	D	0.783	deleterious	N	0.359217858	None	None	N
P/I	0.462	ambiguous	0.509	ambiguous	-0.528	Destabilizing	0.976	D	0.816	deleterious	None	None	None	None	N
P/K	0.8902	likely_pathogenic	0.8842	pathogenic	-1.626	Destabilizing	0.919	D	0.763	deleterious	None	None	None	None	N
P/L	0.247	likely_benign	0.2715	benign	-0.528	Destabilizing	0.896	D	0.773	deleterious	N	0.401160481	None	None	N
P/M	0.536	ambiguous	0.569	pathogenic	-0.631	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
P/N	0.7862	likely_pathogenic	0.7808	pathogenic	-1.974	Destabilizing	0.976	D	0.793	deleterious	None	None	None	None	N
P/Q	0.576	likely_pathogenic	0.5847	pathogenic	-1.824	Destabilizing	0.988	D	0.803	deleterious	None	None	None	None	N
P/R	0.6965	likely_pathogenic	0.6752	pathogenic	-1.485	Destabilizing	0.984	D	0.801	deleterious	N	0.389194048	None	None	N
P/S	0.2388	likely_benign	0.2275	benign	-2.424	Highly Destabilizing	0.251	N	0.592	neutral	N	0.338167795	None	None	N
P/T	0.1868	likely_benign	0.1934	benign	-2.12	Highly Destabilizing	0.811	D	0.763	deleterious	N	0.378360979	None	None	N
P/V	0.2856	likely_benign	0.3251	benign	-0.952	Destabilizing	0.851	D	0.763	deleterious	None	None	None	None	N
P/W	0.8765	likely_pathogenic	0.8753	pathogenic	-1.731	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
P/Y	0.6831	likely_pathogenic	0.6721	pathogenic	-1.372	Destabilizing	0.996	D	0.822	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.