TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24069	72430;72431;72432	chr2:178573927;178573926;178573925	chr2:179438654;179438653;179438652
N2AB	22428	67507;67508;67509	chr2:178573927;178573926;178573925	chr2:179438654;179438653;179438652
N2A	21501	64726;64727;64728	chr2:178573927;178573926;178573925	chr2:179438654;179438653;179438652
N2B	15004	45235;45236;45237	chr2:178573927;178573926;178573925	chr2:179438654;179438653;179438652
Novex-1	15129	45610;45611;45612	chr2:178573927;178573926;178573925	chr2:179438654;179438653;179438652
Novex-2	15196	45811;45812;45813	chr2:178573927;178573926;178573925	chr2:179438654;179438653;179438652
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-131
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.611
• 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
E/G	None	None	0.645	N	0.527	0.494	0.509053020717	gnomAD-4.0.0	1.59294E-06	None	None	None	None	N	None	0	0	None	0	2.78443E-05	None	0	0	0	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
E/A	0.0981	likely_benign	0.1061	benign	-0.287	Destabilizing	0.645	D	0.594	neutral	N	0.488454715	None	None	N
E/C	0.682	likely_pathogenic	0.6865	pathogenic	-0.072	Destabilizing	0.995	D	0.667	neutral	None	None	None	None	N
E/D	0.1044	likely_benign	0.1022	benign	-0.302	Destabilizing	0.002	N	0.245	neutral	N	0.50975861	None	None	N
E/F	0.507	ambiguous	0.5408	ambiguous	-0.173	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	N
E/G	0.1287	likely_benign	0.1314	benign	-0.473	Destabilizing	0.645	D	0.527	neutral	N	0.518537613	None	None	N
E/H	0.3356	likely_benign	0.3406	ambiguous	0.125	Stabilizing	0.995	D	0.581	neutral	None	None	None	None	N
E/I	0.16	likely_benign	0.178	benign	0.163	Stabilizing	0.945	D	0.656	neutral	None	None	None	None	N
E/K	0.107	likely_benign	0.1181	benign	0.36	Stabilizing	0.645	D	0.563	neutral	N	0.490883797	None	None	N
E/L	0.2014	likely_benign	0.2246	benign	0.163	Stabilizing	0.945	D	0.649	neutral	None	None	None	None	N
E/M	0.2544	likely_benign	0.2905	benign	0.16	Stabilizing	0.995	D	0.591	neutral	None	None	None	None	N
E/N	0.1782	likely_benign	0.1847	benign	0.048	Stabilizing	0.809	D	0.567	neutral	None	None	None	None	N
E/P	0.2219	likely_benign	0.2146	benign	0.033	Stabilizing	0.945	D	0.635	neutral	None	None	None	None	N
E/Q	0.1175	likely_benign	0.1215	benign	0.081	Stabilizing	0.864	D	0.54	neutral	N	0.488201225	None	None	N
E/R	0.1903	likely_benign	0.1983	benign	0.574	Stabilizing	0.945	D	0.611	neutral	None	None	None	None	N
E/S	0.1555	likely_benign	0.1594	benign	-0.107	Destabilizing	0.547	D	0.559	neutral	None	None	None	None	N
E/T	0.1411	likely_benign	0.1562	benign	0.046	Stabilizing	0.894	D	0.587	neutral	None	None	None	None	N
E/V	0.1033	likely_benign	0.1164	benign	0.033	Stabilizing	0.928	D	0.607	neutral	N	0.484531149	None	None	N
E/W	0.7505	likely_pathogenic	0.7624	pathogenic	-0.037	Destabilizing	0.995	D	0.671	neutral	None	None	None	None	N
E/Y	0.3991	ambiguous	0.4092	ambiguous	0.069	Stabilizing	0.995	D	0.6	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.