TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2584	7975;7976;7977	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939
N2AB	2584	7975;7976;7977	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939
N2A	2584	7975;7976;7977	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939
N2B	2538	7837;7838;7839	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939
Novex-1	2538	7837;7838;7839	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939
Novex-2	2538	7837;7838;7839	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939
Novex-3	2584	7975;7976;7977	chr2:178773214;178773213;178773212	chr2:179637941;179637940;179637939

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-15
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.3742
• 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
G/E	None	None	1.0	N	0.679	0.382	0.342631996419	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	2.28896E-05	None	0	0	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
G/A	0.5536	ambiguous	0.5135	ambiguous	-0.216	Destabilizing	1.0	D	0.522	neutral	N	0.461092022	None	None	N
G/C	0.6817	likely_pathogenic	0.643	pathogenic	-0.757	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/D	0.3415	ambiguous	0.295	benign	-0.104	Destabilizing	0.921	D	0.532	neutral	None	None	None	None	N
G/E	0.5017	ambiguous	0.4329	ambiguous	-0.226	Destabilizing	1.0	D	0.679	prob.neutral	N	0.47326425	None	None	N
G/F	0.9655	likely_pathogenic	0.9591	pathogenic	-0.739	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
G/H	0.6969	likely_pathogenic	0.6755	pathogenic	-0.481	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
G/I	0.9414	likely_pathogenic	0.9287	pathogenic	-0.185	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
G/K	0.6916	likely_pathogenic	0.6445	pathogenic	-0.687	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
G/L	0.9164	likely_pathogenic	0.9039	pathogenic	-0.185	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/M	0.9452	likely_pathogenic	0.9333	pathogenic	-0.388	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
G/N	0.43	ambiguous	0.3992	ambiguous	-0.347	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
G/P	0.982	likely_pathogenic	0.9807	pathogenic	-0.158	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/Q	0.5763	likely_pathogenic	0.5384	ambiguous	-0.533	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
G/R	0.5557	ambiguous	0.5079	ambiguous	-0.362	Destabilizing	1.0	D	0.73	prob.delet.	N	0.461900665	None	None	N
G/S	0.2204	likely_benign	0.2065	benign	-0.591	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
G/T	0.7205	likely_pathogenic	0.6873	pathogenic	-0.622	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
G/V	0.8902	likely_pathogenic	0.8645	pathogenic	-0.158	Destabilizing	1.0	D	0.755	deleterious	D	0.60164035	None	None	N
G/W	0.8736	likely_pathogenic	0.8551	pathogenic	-0.961	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
G/Y	0.8879	likely_pathogenic	0.8718	pathogenic	-0.571	Destabilizing	1.0	D	0.74	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.