TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21600	65023;65024;65025	chr2:178584843;178584842;178584841	chr2:179449570;179449569;179449568
N2AB	19959	60100;60101;60102	chr2:178584843;178584842;178584841	chr2:179449570;179449569;179449568
N2A	19032	57319;57320;57321	chr2:178584843;178584842;178584841	chr2:179449570;179449569;179449568
N2B	12535	37828;37829;37830	chr2:178584843;178584842;178584841	chr2:179449570;179449569;179449568
Novex-1	12660	38203;38204;38205	chr2:178584843;178584842;178584841	chr2:179449570;179449569;179449568
Novex-2	12727	38404;38405;38406	chr2:178584843;178584842;178584841	chr2:179449570;179449569;179449568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-44
• Domain position: 42
• Structural Position: 43
• Q(SASA): 0.0673
• 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
C/R	rs1436243584	-1.038	0.99	N	0.795	0.42	0.726150275566	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
C/R	rs1436243584	-1.038	0.99	N	0.795	0.42	0.726150275566	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73551E-04	0	1.1595E-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
C/A	0.5873	likely_pathogenic	0.6198	pathogenic	-1.345	Destabilizing	0.717	D	0.551	neutral	None	None	None	None	N
C/D	0.9572	likely_pathogenic	0.9655	pathogenic	-1.319	Destabilizing	0.993	D	0.792	deleterious	None	None	None	None	N
C/E	0.9384	likely_pathogenic	0.9421	pathogenic	-1.074	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
C/F	0.4905	ambiguous	0.5317	ambiguous	-0.87	Destabilizing	0.032	N	0.518	neutral	N	0.481365995	None	None	N
C/G	0.3878	ambiguous	0.4206	ambiguous	-1.684	Destabilizing	0.97	D	0.761	deleterious	N	0.473557604	None	None	N
C/H	0.6891	likely_pathogenic	0.7168	pathogenic	-2.0	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
C/I	0.8185	likely_pathogenic	0.8351	pathogenic	-0.423	Destabilizing	0.915	D	0.691	prob.neutral	None	None	None	None	N
C/K	0.8063	likely_pathogenic	0.8275	pathogenic	-0.687	Destabilizing	0.978	D	0.789	deleterious	None	None	None	None	N
C/L	0.6663	likely_pathogenic	0.7118	pathogenic	-0.423	Destabilizing	0.754	D	0.605	neutral	None	None	None	None	N
C/M	0.6876	likely_pathogenic	0.7305	pathogenic	0.082	Stabilizing	0.994	D	0.682	prob.neutral	None	None	None	None	N
C/N	0.7585	likely_pathogenic	0.7716	pathogenic	-1.331	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
C/P	0.9987	likely_pathogenic	0.9988	pathogenic	-0.71	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
C/Q	0.6341	likely_pathogenic	0.6525	pathogenic	-0.801	Destabilizing	0.993	D	0.787	deleterious	None	None	None	None	N
C/R	0.4184	ambiguous	0.4529	ambiguous	-1.301	Destabilizing	0.99	D	0.795	deleterious	N	0.365288186	None	None	N
C/S	0.524	ambiguous	0.5462	ambiguous	-1.55	Destabilizing	0.904	D	0.655	neutral	N	0.442479533	None	None	N
C/T	0.7198	likely_pathogenic	0.7505	pathogenic	-1.13	Destabilizing	0.978	D	0.687	prob.neutral	None	None	None	None	N
C/V	0.693	likely_pathogenic	0.7188	pathogenic	-0.71	Destabilizing	0.86	D	0.641	neutral	None	None	None	None	N
C/W	0.7679	likely_pathogenic	0.7853	pathogenic	-1.34	Destabilizing	0.997	D	0.706	prob.neutral	N	0.506357653	None	None	N
C/Y	0.526	ambiguous	0.5631	ambiguous	-1.069	Destabilizing	0.89	D	0.7	prob.neutral	N	0.504992216	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.