TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35320	106183;106184;106185	chr2:178530657;178530656;178530655	chr2:179395384;179395383;179395382
N2AB	33679	101260;101261;101262	chr2:178530657;178530656;178530655	chr2:179395384;179395383;179395382
N2A	32752	98479;98480;98481	chr2:178530657;178530656;178530655	chr2:179395384;179395383;179395382
N2B	26255	78988;78989;78990	chr2:178530657;178530656;178530655	chr2:179395384;179395383;179395382
Novex-1	26380	79363;79364;79365	chr2:178530657;178530656;178530655	chr2:179395384;179395383;179395382
Novex-2	26447	79564;79565;79566	chr2:178530657;178530656;178530655	chr2:179395384;179395383;179395382
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-165
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1485
• 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/C	rs1558988630	None	0.997	N	0.649	0.292	0.467585353272	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
Y/C	rs1558988630	None	0.997	N	0.649	0.292	0.467585353272	gnomAD-4.0.0	1.36827E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7337E-04	8.99394E-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
Y/A	0.8797	likely_pathogenic	0.8157	pathogenic	-2.666	Highly Destabilizing	0.842	D	0.582	neutral	None	None	None	None	N
Y/C	0.3424	ambiguous	0.2796	benign	-1.138	Destabilizing	0.997	D	0.649	neutral	N	0.481672138	None	None	N
Y/D	0.8069	likely_pathogenic	0.7203	pathogenic	-1.411	Destabilizing	0.966	D	0.669	neutral	N	0.463567883	None	None	N
Y/E	0.8659	likely_pathogenic	0.797	pathogenic	-1.304	Destabilizing	0.974	D	0.641	neutral	None	None	None	None	N
Y/F	0.1207	likely_benign	0.106	benign	-1.103	Destabilizing	0.012	N	0.352	neutral	N	0.473321649	None	None	N
Y/G	0.8082	likely_pathogenic	0.733	pathogenic	-2.998	Highly Destabilizing	0.974	D	0.65	neutral	None	None	None	None	N
Y/H	0.3004	likely_benign	0.2326	benign	-1.279	Destabilizing	0.989	D	0.555	neutral	N	0.447919163	None	None	N
Y/I	0.7049	likely_pathogenic	0.5982	pathogenic	-1.63	Destabilizing	0.728	D	0.544	neutral	None	None	None	None	N
Y/K	0.7877	likely_pathogenic	0.6958	pathogenic	-1.336	Destabilizing	0.974	D	0.639	neutral	None	None	None	None	N
Y/L	0.5661	likely_pathogenic	0.4793	ambiguous	-1.63	Destabilizing	0.016	N	0.401	neutral	None	None	None	None	N
Y/M	0.7436	likely_pathogenic	0.669	pathogenic	-1.23	Destabilizing	0.949	D	0.603	neutral	None	None	None	None	N
Y/N	0.4356	ambiguous	0.3434	ambiguous	-1.636	Destabilizing	0.989	D	0.657	neutral	N	0.456477538	None	None	N
Y/P	0.9973	likely_pathogenic	0.996	pathogenic	-1.975	Destabilizing	0.037	N	0.539	neutral	None	None	None	None	N
Y/Q	0.7222	likely_pathogenic	0.6184	pathogenic	-1.6	Destabilizing	0.991	D	0.605	neutral	None	None	None	None	N
Y/R	0.6371	likely_pathogenic	0.5381	ambiguous	-0.823	Destabilizing	0.974	D	0.656	neutral	None	None	None	None	N
Y/S	0.5493	ambiguous	0.452	ambiguous	-2.214	Highly Destabilizing	0.966	D	0.629	neutral	N	0.439739182	None	None	N
Y/T	0.7884	likely_pathogenic	0.6997	pathogenic	-2.016	Highly Destabilizing	0.974	D	0.632	neutral	None	None	None	None	N
Y/V	0.6706	likely_pathogenic	0.574	pathogenic	-1.975	Destabilizing	0.728	D	0.529	neutral	None	None	None	None	N
Y/W	0.5301	ambiguous	0.4752	ambiguous	-0.542	Destabilizing	0.998	D	0.548	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.