TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16944	51055;51056;51057	chr2:178611399;178611398;178611397	chr2:179476126;179476125;179476124
N2AB	15303	46132;46133;46134	chr2:178611399;178611398;178611397	chr2:179476126;179476125;179476124
N2A	14376	43351;43352;43353	chr2:178611399;178611398;178611397	chr2:179476126;179476125;179476124
N2B	7879	23860;23861;23862	chr2:178611399;178611398;178611397	chr2:179476126;179476125;179476124
Novex-1	8004	24235;24236;24237	chr2:178611399;178611398;178611397	chr2:179476126;179476125;179476124
Novex-2	8071	24436;24437;24438	chr2:178611399;178611398;178611397	chr2:179476126;179476125;179476124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-11
• Domain position: 93
• Structural Position: 125
• Q(SASA): 0.7306
• Predicted PPI site: I

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	rs758389457	-0.204	0.999	N	0.673	0.391	0.489728331402	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs758389457	-0.204	0.999	N	0.673	0.391	0.489728331402	gnomAD-4.0.0	1.59333E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4332E-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
E/A	0.3003	likely_benign	0.3199	benign	-0.524	Destabilizing	0.997	D	0.8	deleterious	N	0.503501469	None	None	I
E/C	0.9228	likely_pathogenic	0.9289	pathogenic	-0.197	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
E/D	0.1535	likely_benign	0.1629	benign	-0.6	Destabilizing	0.997	D	0.667	prob.neutral	N	0.465028529	None	None	I
E/F	0.9268	likely_pathogenic	0.9262	pathogenic	-0.164	Destabilizing	1.0	D	0.724	deleterious	None	None	None	None	I
E/G	0.2077	likely_benign	0.2248	benign	-0.797	Destabilizing	0.999	D	0.673	prob.neutral	N	0.506189568	None	None	I
E/H	0.7003	likely_pathogenic	0.7337	pathogenic	-0.132	Destabilizing	1.0	D	0.703	prob.delet.	None	None	None	None	I
E/I	0.7194	likely_pathogenic	0.7183	pathogenic	0.188	Stabilizing	0.999	D	0.725	deleterious	None	None	None	None	I
E/K	0.2354	likely_benign	0.2594	benign	0.054	Stabilizing	0.997	D	0.745	deleterious	N	0.463384175	None	None	I
E/L	0.7122	likely_pathogenic	0.7247	pathogenic	0.188	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
E/M	0.7395	likely_pathogenic	0.7494	pathogenic	0.342	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/N	0.4002	ambiguous	0.4313	ambiguous	-0.425	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
E/P	0.7074	likely_pathogenic	0.7103	pathogenic	-0.028	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
E/Q	0.2182	likely_benign	0.245	benign	-0.336	Destabilizing	0.999	D	0.719	prob.delet.	N	0.495215313	None	None	I
E/R	0.3947	ambiguous	0.4333	ambiguous	0.304	Stabilizing	0.999	D	0.804	deleterious	None	None	None	None	I
E/S	0.3221	likely_benign	0.3494	ambiguous	-0.597	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	I
E/T	0.402	ambiguous	0.4313	ambiguous	-0.371	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
E/V	0.481	ambiguous	0.4881	ambiguous	-0.028	Destabilizing	0.999	D	0.719	prob.delet.	D	0.57382766	None	None	I
E/W	0.9621	likely_pathogenic	0.964	pathogenic	0.054	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
E/Y	0.8511	likely_pathogenic	0.8572	pathogenic	0.089	Stabilizing	1.0	D	0.725	deleterious	None	None	None	None	I

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.