TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23494	70705;70706;70707	chr2:178575652;178575651;178575650	chr2:179440379;179440378;179440377
N2AB	21853	65782;65783;65784	chr2:178575652;178575651;178575650	chr2:179440379;179440378;179440377
N2A	20926	63001;63002;63003	chr2:178575652;178575651;178575650	chr2:179440379;179440378;179440377
N2B	14429	43510;43511;43512	chr2:178575652;178575651;178575650	chr2:179440379;179440378;179440377
Novex-1	14554	43885;43886;43887	chr2:178575652;178575651;178575650	chr2:179440379;179440378;179440377
Novex-2	14621	44086;44087;44088	chr2:178575652;178575651;178575650	chr2:179440379;179440378;179440377
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-58
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.2096
• 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
Y/H	rs72646888	None	0.741	N	0.539	0.291	0.384752662912	gnomAD-4.0.0	6.84286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09597E-06	0	1.65684E-05
Y/N	None	None	0.484	N	0.615	0.429	0.683845495215	gnomAD-4.0.0	6.84286E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99552E-07	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
Y/A	0.4748	ambiguous	0.5548	ambiguous	-2.082	Highly Destabilizing	0.035	N	0.536	neutral	None	None	None	None	N
Y/C	0.1114	likely_benign	0.1264	benign	-0.949	Destabilizing	0.001	N	0.512	neutral	N	0.469461065	None	None	N
Y/D	0.7847	likely_pathogenic	0.8519	pathogenic	-1.008	Destabilizing	0.741	D	0.643	neutral	D	0.525181933	None	None	N
Y/E	0.8459	likely_pathogenic	0.8988	pathogenic	-0.895	Destabilizing	0.791	D	0.633	neutral	None	None	None	None	N
Y/F	0.0621	likely_benign	0.065	benign	-0.677	Destabilizing	None	N	0.167	neutral	N	0.430998677	None	None	N
Y/G	0.5853	likely_pathogenic	0.6574	pathogenic	-2.423	Highly Destabilizing	0.149	N	0.613	neutral	None	None	None	None	N
Y/H	0.2608	likely_benign	0.3034	benign	-0.886	Destabilizing	0.741	D	0.539	neutral	N	0.474539244	None	None	N
Y/I	0.3869	ambiguous	0.4871	ambiguous	-1.037	Destabilizing	0.081	N	0.519	neutral	None	None	None	None	N
Y/K	0.8542	likely_pathogenic	0.8976	pathogenic	-1.245	Destabilizing	0.555	D	0.632	neutral	None	None	None	None	N
Y/L	0.3839	ambiguous	0.4453	ambiguous	-1.037	Destabilizing	None	N	0.303	neutral	None	None	None	None	N
Y/M	0.4911	ambiguous	0.5655	pathogenic	-0.782	Destabilizing	0.38	N	0.566	neutral	None	None	None	None	N
Y/N	0.4723	ambiguous	0.5868	pathogenic	-1.712	Destabilizing	0.484	N	0.615	neutral	N	0.513572138	None	None	N
Y/P	0.9838	likely_pathogenic	0.9889	pathogenic	-1.382	Destabilizing	0.791	D	0.635	neutral	None	None	None	None	N
Y/Q	0.6565	likely_pathogenic	0.7383	pathogenic	-1.55	Destabilizing	0.791	D	0.556	neutral	None	None	None	None	N
Y/R	0.732	likely_pathogenic	0.7848	pathogenic	-0.934	Destabilizing	0.555	D	0.619	neutral	None	None	None	None	N
Y/S	0.3328	likely_benign	0.4148	ambiguous	-2.188	Highly Destabilizing	0.117	N	0.59	neutral	N	0.492581047	None	None	N
Y/T	0.5324	ambiguous	0.6454	pathogenic	-1.972	Destabilizing	0.149	N	0.597	neutral	None	None	None	None	N
Y/V	0.2926	likely_benign	0.3649	ambiguous	-1.382	Destabilizing	0.035	N	0.488	neutral	None	None	None	None	N
Y/W	0.296	likely_benign	0.2979	benign	-0.28	Destabilizing	0.791	D	0.551	neutral	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.