TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5321	16186;16187;16188	chr2:178733332;178733331;178733330	chr2:179598059;179598058;179598057
N2AB	5004	15235;15236;15237	chr2:178733332;178733331;178733330	chr2:179598059;179598058;179598057
N2A	4077	12454;12455;12456	chr2:178733332;178733331;178733330	chr2:179598059;179598058;179598057
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-36
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.4195
• 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	None	None	0.999	N	0.476	0.484	0.635582896387	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.4993	ambiguous	0.4963	ambiguous	-1.274	Destabilizing	0.969	D	0.393	neutral	None	None	None	None	N
Y/C	0.2202	likely_benign	0.1875	benign	-0.327	Destabilizing	0.999	D	0.476	neutral	N	0.509494959	None	None	N
Y/D	0.4326	ambiguous	0.4029	ambiguous	0.615	Stabilizing	0.996	D	0.503	neutral	N	0.441423793	None	None	N
Y/E	0.7574	likely_pathogenic	0.746	pathogenic	0.647	Stabilizing	0.997	D	0.45	neutral	None	None	None	None	N
Y/F	0.1233	likely_benign	0.1222	benign	-0.432	Destabilizing	0.92	D	0.371	neutral	N	0.492859091	None	None	N
Y/G	0.4907	ambiguous	0.4978	ambiguous	-1.526	Destabilizing	0.997	D	0.457	neutral	None	None	None	None	N
Y/H	0.241	likely_benign	0.218	benign	-0.128	Destabilizing	0.996	D	0.411	neutral	N	0.442620588	None	None	N
Y/I	0.4681	ambiguous	0.4299	ambiguous	-0.574	Destabilizing	0.884	D	0.337	neutral	None	None	None	None	N
Y/K	0.7693	likely_pathogenic	0.7502	pathogenic	-0.34	Destabilizing	0.997	D	0.437	neutral	None	None	None	None	N
Y/L	0.3465	ambiguous	0.3235	benign	-0.574	Destabilizing	0.007	N	0.155	neutral	None	None	None	None	N
Y/M	0.662	likely_pathogenic	0.6489	pathogenic	-0.419	Destabilizing	0.982	D	0.426	neutral	None	None	None	None	N
Y/N	0.2086	likely_benign	0.1945	benign	-0.589	Destabilizing	0.996	D	0.489	neutral	N	0.437780413	None	None	N
Y/P	0.6228	likely_pathogenic	0.6466	pathogenic	-0.792	Destabilizing	0.997	D	0.505	neutral	None	None	None	None	N
Y/Q	0.589	likely_pathogenic	0.5613	ambiguous	-0.494	Destabilizing	0.997	D	0.434	neutral	None	None	None	None	N
Y/R	0.5698	likely_pathogenic	0.5555	ambiguous	-0.028	Destabilizing	0.997	D	0.483	neutral	None	None	None	None	N
Y/S	0.1876	likely_benign	0.1838	benign	-1.12	Destabilizing	0.996	D	0.432	neutral	N	0.392249425	None	None	N
Y/T	0.4417	ambiguous	0.4318	ambiguous	-0.995	Destabilizing	0.969	D	0.415	neutral	None	None	None	None	N
Y/V	0.401	ambiguous	0.3783	ambiguous	-0.792	Destabilizing	0.759	D	0.33	neutral	None	None	None	None	N
Y/W	0.5593	ambiguous	0.5517	ambiguous	-0.303	Destabilizing	0.999	D	0.404	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.