TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17559	52900;52901;52902	chr2:178608208;178608207;178608206	chr2:179472935;179472934;179472933
N2AB	15918	47977;47978;47979	chr2:178608208;178608207;178608206	chr2:179472935;179472934;179472933
N2A	14991	45196;45197;45198	chr2:178608208;178608207;178608206	chr2:179472935;179472934;179472933
N2B	8494	25705;25706;25707	chr2:178608208;178608207;178608206	chr2:179472935;179472934;179472933
Novex-1	8619	26080;26081;26082	chr2:178608208;178608207;178608206	chr2:179472935;179472934;179472933
Novex-2	8686	26281;26282;26283	chr2:178608208;178608207;178608206	chr2:179472935;179472934;179472933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-15
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.2401
• 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/A	rs2055393436	None	0.994	N	0.633	0.188	0.340032825777	gnomAD-4.0.0	1.20032E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-05	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	0.4944	ambiguous	0.4167	ambiguous	-0.615	Destabilizing	0.994	D	0.633	neutral	N	0.485808828	None	None	N
S/C	0.5032	ambiguous	0.3556	ambiguous	-0.404	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/D	0.9921	likely_pathogenic	0.9878	pathogenic	-0.851	Destabilizing	0.998	D	0.664	prob.neutral	None	None	None	None	N
S/E	0.9969	likely_pathogenic	0.9956	pathogenic	-0.726	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
S/F	0.9944	likely_pathogenic	0.9876	pathogenic	-0.385	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
S/G	0.5697	likely_pathogenic	0.4876	ambiguous	-0.987	Destabilizing	0.998	D	0.703	prob.delet.	None	None	None	None	N
S/H	0.9934	likely_pathogenic	0.9897	pathogenic	-1.433	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
S/I	0.9762	likely_pathogenic	0.956	pathogenic	0.304	Stabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
S/K	0.9995	likely_pathogenic	0.9993	pathogenic	-0.565	Destabilizing	0.998	D	0.663	prob.neutral	None	None	None	None	N
S/L	0.8956	likely_pathogenic	0.8271	pathogenic	0.304	Stabilizing	0.999	D	0.781	deleterious	N	0.479755213	None	None	N
S/M	0.9345	likely_pathogenic	0.8846	pathogenic	0.29	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/N	0.9683	likely_pathogenic	0.9486	pathogenic	-0.92	Destabilizing	0.998	D	0.694	prob.delet.	None	None	None	None	N
S/P	0.995	likely_pathogenic	0.9896	pathogenic	0.034	Stabilizing	0.999	D	0.84	deleterious	N	0.5140813	None	None	N
S/Q	0.9956	likely_pathogenic	0.9935	pathogenic	-0.775	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
S/R	0.9989	likely_pathogenic	0.9985	pathogenic	-0.805	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
S/T	0.2262	likely_benign	0.1608	benign	-0.69	Destabilizing	0.997	D	0.692	prob.delet.	N	0.476802751	None	None	N
S/V	0.9301	likely_pathogenic	0.8815	pathogenic	0.034	Stabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
S/W	0.9956	likely_pathogenic	0.9931	pathogenic	-0.589	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
S/Y	0.9942	likely_pathogenic	0.9899	pathogenic	-0.205	Destabilizing	0.999	D	0.883	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.