TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8145	24658;24659;24660	chr2:178718767;178718766;178718765	chr2:179583494;179583493;179583492
N2AB	7828	23707;23708;23709	chr2:178718767;178718766;178718765	chr2:179583494;179583493;179583492
N2A	6901	20926;20927;20928	chr2:178718767;178718766;178718765	chr2:179583494;179583493;179583492
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-66
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.226
• 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
S/N	rs1560647433	None	0.896	N	0.518	0.271	0.278143212241	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
S/N	rs1560647433	None	0.896	N	0.518	0.271	0.278143212241	gnomAD-4.0.0	2.05264E-06	None	None	None	None	N	None	0	2.23594E-05	None	0	0	None	0	0	1.79897E-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
S/A	0.1076	likely_benign	0.123	benign	-0.688	Destabilizing	0.06	N	0.182	neutral	None	None	None	None	N
S/C	0.2847	likely_benign	0.329	benign	-0.342	Destabilizing	0.999	D	0.694	prob.neutral	D	0.525818995	None	None	N
S/D	0.6081	likely_pathogenic	0.6442	pathogenic	0.261	Stabilizing	0.919	D	0.509	neutral	None	None	None	None	N
S/E	0.6829	likely_pathogenic	0.7401	pathogenic	0.306	Stabilizing	0.919	D	0.525	neutral	None	None	None	None	N
S/F	0.5738	likely_pathogenic	0.6567	pathogenic	-0.786	Destabilizing	0.988	D	0.778	deleterious	None	None	None	None	N
S/G	0.0943	likely_benign	0.1218	benign	-0.973	Destabilizing	0.78	D	0.569	neutral	N	0.501674352	None	None	N
S/H	0.6381	likely_pathogenic	0.7091	pathogenic	-1.328	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
S/I	0.4218	ambiguous	0.507	ambiguous	-0.024	Destabilizing	0.968	D	0.732	prob.delet.	N	0.50918277	None	None	N
S/K	0.7863	likely_pathogenic	0.8561	pathogenic	-0.29	Destabilizing	0.919	D	0.53	neutral	None	None	None	None	N
S/L	0.2549	likely_benign	0.2996	benign	-0.024	Destabilizing	0.851	D	0.657	neutral	None	None	None	None	N
S/M	0.3442	ambiguous	0.3952	ambiguous	0.049	Stabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
S/N	0.2352	likely_benign	0.2777	benign	-0.375	Destabilizing	0.896	D	0.518	neutral	N	0.515904267	None	None	N
S/P	0.6606	likely_pathogenic	0.6781	pathogenic	-0.211	Destabilizing	0.988	D	0.689	prob.neutral	None	None	None	None	N
S/Q	0.6618	likely_pathogenic	0.736	pathogenic	-0.388	Destabilizing	0.988	D	0.549	neutral	None	None	None	None	N
S/R	0.703	likely_pathogenic	0.8098	pathogenic	-0.362	Destabilizing	0.968	D	0.696	prob.neutral	N	0.4989521	None	None	N
S/T	0.125	likely_benign	0.1283	benign	-0.401	Destabilizing	0.103	N	0.346	neutral	N	0.485936727	None	None	N
S/V	0.4466	ambiguous	0.4973	ambiguous	-0.211	Destabilizing	0.851	D	0.655	neutral	None	None	None	None	N
S/W	0.6784	likely_pathogenic	0.7472	pathogenic	-0.794	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
S/Y	0.4742	ambiguous	0.55	ambiguous	-0.478	Destabilizing	0.996	D	0.779	deleterious	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.