TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31795	95608;95609;95610	chr2:178545853;178545852;178545851	chr2:179410580;179410579;179410578
N2AB	30154	90685;90686;90687	chr2:178545853;178545852;178545851	chr2:179410580;179410579;179410578
N2A	29227	87904;87905;87906	chr2:178545853;178545852;178545851	chr2:179410580;179410579;179410578
N2B	22730	68413;68414;68415	chr2:178545853;178545852;178545851	chr2:179410580;179410579;179410578
Novex-1	22855	68788;68789;68790	chr2:178545853;178545852;178545851	chr2:179410580;179410579;179410578
Novex-2	22922	68989;68990;68991	chr2:178545853;178545852;178545851	chr2:179410580;179410579;179410578
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: Fn3-119
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3397
• 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/Q	None	None	0.999	N	0.798	0.164	0.240491677333	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/V	rs1441773765	0.449	0.999	N	0.769	0.508	0.590258251349	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/V	rs1441773765	0.449	0.999	N	0.769	0.508	0.590258251349	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	2.28645E-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
E/A	0.2045	likely_benign	0.2366	benign	-0.695	Destabilizing	0.997	D	0.816	deleterious	N	0.480786079	None	None	N
E/C	0.84	likely_pathogenic	0.8608	pathogenic	-0.356	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/D	0.201	likely_benign	0.2084	benign	-0.833	Destabilizing	0.997	D	0.771	deleterious	N	0.513571627	None	None	N
E/F	0.7446	likely_pathogenic	0.769	pathogenic	0.176	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/G	0.3829	ambiguous	0.4271	ambiguous	-1.079	Destabilizing	0.999	D	0.742	deleterious	N	0.489268776	None	None	N
E/H	0.6421	likely_pathogenic	0.6682	pathogenic	0.135	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/I	0.2877	likely_benign	0.3202	benign	0.359	Stabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
E/K	0.3658	ambiguous	0.3958	ambiguous	-0.187	Destabilizing	0.997	D	0.84	deleterious	N	0.484331251	None	None	N
E/L	0.371	ambiguous	0.402	ambiguous	0.359	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
E/M	0.4201	ambiguous	0.4646	ambiguous	0.645	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/N	0.3825	ambiguous	0.4064	ambiguous	-0.913	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
E/P	0.7043	likely_pathogenic	0.7395	pathogenic	0.029	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/Q	0.1906	likely_benign	0.2043	benign	-0.747	Destabilizing	0.999	D	0.798	deleterious	N	0.517209365	None	None	N
E/R	0.5393	ambiguous	0.5708	pathogenic	0.182	Stabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
E/S	0.2718	likely_benign	0.307	benign	-1.203	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
E/T	0.2275	likely_benign	0.2646	benign	-0.864	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/V	0.178	likely_benign	0.2044	benign	0.029	Stabilizing	0.999	D	0.769	deleterious	N	0.476800061	None	None	N
E/W	0.9412	likely_pathogenic	0.9506	pathogenic	0.543	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Y	0.6989	likely_pathogenic	0.7314	pathogenic	0.491	Stabilizing	1.0	D	0.845	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.