TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33509	100750;100751;100752	chr2:178536222;178536221;178536220	chr2:179400949;179400948;179400947
N2AB	31868	95827;95828;95829	chr2:178536222;178536221;178536220	chr2:179400949;179400948;179400947
N2A	30941	93046;93047;93048	chr2:178536222;178536221;178536220	chr2:179400949;179400948;179400947
N2B	24444	73555;73556;73557	chr2:178536222;178536221;178536220	chr2:179400949;179400948;179400947
Novex-1	24569	73930;73931;73932	chr2:178536222;178536221;178536220	chr2:179400949;179400948;179400947
Novex-2	24636	74131;74132;74133	chr2:178536222;178536221;178536220	chr2:179400949;179400948;179400947
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-158
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.3451
• 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
Y/H	rs1404850899	-0.987	0.903	N	0.389	0.235	0.400756358115	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
Y/H	rs1404850899	-0.987	0.903	N	0.389	0.235	0.400756358115	gnomAD-4.0.0	1.59254E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86023E-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
Y/A	0.7386	likely_pathogenic	0.6592	pathogenic	-1.233	Destabilizing	0.921	D	0.535	neutral	None	None	None	None	N
Y/C	0.3048	likely_benign	0.242	benign	-0.101	Destabilizing	0.997	D	0.573	neutral	N	0.510662687	None	None	N
Y/D	0.7502	likely_pathogenic	0.6909	pathogenic	0.63	Stabilizing	0.884	D	0.55	neutral	N	0.426198651	None	None	N
Y/E	0.8525	likely_pathogenic	0.8059	pathogenic	0.632	Stabilizing	0.953	D	0.479	neutral	None	None	None	None	N
Y/F	0.0918	likely_benign	0.0757	benign	-0.649	Destabilizing	0.002	N	0.231	neutral	N	0.443688334	None	None	N
Y/G	0.7444	likely_pathogenic	0.6865	pathogenic	-1.464	Destabilizing	0.852	D	0.524	neutral	None	None	None	None	N
Y/H	0.2486	likely_benign	0.2094	benign	-0.195	Destabilizing	0.903	D	0.389	neutral	N	0.499714975	None	None	N
Y/I	0.7717	likely_pathogenic	0.6534	pathogenic	-0.612	Destabilizing	0.282	N	0.433	neutral	None	None	None	None	N
Y/K	0.81	likely_pathogenic	0.7727	pathogenic	-0.119	Destabilizing	0.71	D	0.487	neutral	None	None	None	None	N
Y/L	0.7044	likely_pathogenic	0.6427	pathogenic	-0.612	Destabilizing	0.101	N	0.519	neutral	None	None	None	None	N
Y/M	0.8254	likely_pathogenic	0.7637	pathogenic	-0.302	Destabilizing	0.979	D	0.433	neutral	None	None	None	None	N
Y/N	0.4323	ambiguous	0.3481	ambiguous	-0.251	Destabilizing	0.119	N	0.432	neutral	N	0.491383493	None	None	N
Y/P	0.8798	likely_pathogenic	0.7699	pathogenic	-0.802	Destabilizing	0.992	D	0.574	neutral	None	None	None	None	N
Y/Q	0.7007	likely_pathogenic	0.6312	pathogenic	-0.244	Destabilizing	0.925	D	0.427	neutral	None	None	None	None	N
Y/R	0.6756	likely_pathogenic	0.6516	pathogenic	0.251	Stabilizing	0.945	D	0.529	neutral	None	None	None	None	N
Y/S	0.5036	ambiguous	0.4293	ambiguous	-0.775	Destabilizing	0.813	D	0.491	neutral	N	0.439415877	None	None	N
Y/T	0.8307	likely_pathogenic	0.7555	pathogenic	-0.681	Destabilizing	0.953	D	0.471	neutral	None	None	None	None	N
Y/V	0.6886	likely_pathogenic	0.5867	pathogenic	-0.802	Destabilizing	0.852	D	0.486	neutral	None	None	None	None	N
Y/W	0.4685	ambiguous	0.4615	ambiguous	-0.597	Destabilizing	0.996	D	0.397	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.