TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13977	42154;42155;42156	chr2:178635260;178635259;178635258	chr2:179499987;179499986;179499985
N2AB	12336	37231;37232;37233	chr2:178635260;178635259;178635258	chr2:179499987;179499986;179499985
N2A	11409	34450;34451;34452	chr2:178635260;178635259;178635258	chr2:179499987;179499986;179499985
N2B	4912	14959;14960;14961	chr2:178635260;178635259;178635258	chr2:179499987;179499986;179499985
Novex-1	5037	15334;15335;15336	chr2:178635260;178635259;178635258	chr2:179499987;179499986;179499985
Novex-2	5104	15535;15536;15537	chr2:178635260;178635259;178635258	chr2:179499987;179499986;179499985
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-90
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5185
• 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/F	None	None	0.016	N	0.338	0.095	0.200317383148	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.8012	likely_pathogenic	0.7756	pathogenic	-1.281	Destabilizing	0.745	D	0.374	neutral	None	None	None	None	N
Y/C	0.5116	ambiguous	0.4672	ambiguous	-0.182	Destabilizing	0.998	D	0.273	neutral	N	0.434819419	None	None	N
Y/D	0.78	likely_pathogenic	0.7752	pathogenic	0.191	Stabilizing	0.974	D	0.441	neutral	N	0.433512679	None	None	N
Y/E	0.9256	likely_pathogenic	0.9	pathogenic	0.206	Stabilizing	0.935	D	0.379	neutral	None	None	None	None	N
Y/F	0.1527	likely_benign	0.1421	benign	-0.561	Destabilizing	0.016	N	0.338	neutral	N	0.433630747	None	None	N
Y/G	0.785	likely_pathogenic	0.7729	pathogenic	-1.52	Destabilizing	0.935	D	0.433	neutral	None	None	None	None	N
Y/H	0.5969	likely_pathogenic	0.5245	ambiguous	-0.201	Destabilizing	0.991	D	0.293	neutral	N	0.434731397	None	None	N
Y/I	0.7875	likely_pathogenic	0.759	pathogenic	-0.622	Destabilizing	0.594	D	0.358	neutral	None	None	None	None	N
Y/K	0.9214	likely_pathogenic	0.9026	pathogenic	-0.376	Destabilizing	0.935	D	0.403	neutral	None	None	None	None	N
Y/L	0.6528	likely_pathogenic	0.6538	pathogenic	-0.622	Destabilizing	0.594	D	0.366	neutral	None	None	None	None	N
Y/M	0.831	likely_pathogenic	0.8206	pathogenic	-0.413	Destabilizing	0.981	D	0.285	neutral	None	None	None	None	N
Y/N	0.554	ambiguous	0.5186	ambiguous	-0.618	Destabilizing	0.974	D	0.423	neutral	N	0.433832052	None	None	N
Y/P	0.878	likely_pathogenic	0.851	pathogenic	-0.827	Destabilizing	0.994	D	0.436	neutral	None	None	None	None	N
Y/Q	0.8942	likely_pathogenic	0.8626	pathogenic	-0.57	Destabilizing	0.994	D	0.355	neutral	None	None	None	None	N
Y/R	0.8096	likely_pathogenic	0.7707	pathogenic	-0.02	Destabilizing	0.981	D	0.397	neutral	None	None	None	None	N
Y/S	0.5529	ambiguous	0.5358	ambiguous	-1.024	Destabilizing	0.728	D	0.327	neutral	N	0.428644222	None	None	N
Y/T	0.7216	likely_pathogenic	0.7318	pathogenic	-0.921	Destabilizing	0.087	N	0.265	neutral	None	None	None	None	N
Y/V	0.624	likely_pathogenic	0.5862	pathogenic	-0.827	Destabilizing	0.038	N	0.149	neutral	None	None	None	None	N
Y/W	0.6335	likely_pathogenic	0.5925	pathogenic	-0.492	Destabilizing	0.994	D	0.29	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.