TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26856	80791;80792;80793	chr2:178565566;178565565;178565564	chr2:179430293;179430292;179430291
N2AB	25215	75868;75869;75870	chr2:178565566;178565565;178565564	chr2:179430293;179430292;179430291
N2A	24288	73087;73088;73089	chr2:178565566;178565565;178565564	chr2:179430293;179430292;179430291
N2B	17791	53596;53597;53598	chr2:178565566;178565565;178565564	chr2:179430293;179430292;179430291
Novex-1	17916	53971;53972;53973	chr2:178565566;178565565;178565564	chr2:179430293;179430292;179430291
Novex-2	17983	54172;54173;54174	chr2:178565566;178565565;178565564	chr2:179430293;179430292;179430291
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: Fn3-83
• Domain position: 77
• Structural Position: 111
• Q(SASA): 0.3192
• 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/N	rs773473233	-1.419	0.81	N	0.617	0.398	0.465975295344	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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	0.3284	likely_benign	0.3326	benign	-2.415	Highly Destabilizing	0.617	D	0.5	neutral	None	None	None	None	N
Y/C	0.0902	likely_benign	0.0825	benign	-0.954	Destabilizing	0.99	D	0.605	neutral	N	0.46247359	None	None	N
Y/D	0.4152	ambiguous	0.389	ambiguous	-1.311	Destabilizing	0.379	N	0.599	neutral	N	0.481232709	None	None	N
Y/E	0.4984	ambiguous	0.4911	ambiguous	-1.164	Destabilizing	0.005	N	0.354	neutral	None	None	None	None	N
Y/F	0.0628	likely_benign	0.0608	benign	-0.757	Destabilizing	0.002	N	0.151	neutral	N	0.433670836	None	None	N
Y/G	0.4536	ambiguous	0.4401	ambiguous	-2.771	Highly Destabilizing	0.617	D	0.585	neutral	None	None	None	None	N
Y/H	0.148	likely_benign	0.1421	benign	-1.035	Destabilizing	0.896	D	0.541	neutral	N	0.43940473	None	None	N
Y/I	0.2069	likely_benign	0.2041	benign	-1.293	Destabilizing	0.447	N	0.531	neutral	None	None	None	None	N
Y/K	0.405	ambiguous	0.4268	ambiguous	-1.266	Destabilizing	0.447	N	0.601	neutral	None	None	None	None	N
Y/L	0.3175	likely_benign	0.3253	benign	-1.293	Destabilizing	0.25	N	0.433	neutral	None	None	None	None	N
Y/M	0.3824	ambiguous	0.3992	ambiguous	-0.938	Destabilizing	0.92	D	0.569	neutral	None	None	None	None	N
Y/N	0.2215	likely_benign	0.1938	benign	-1.729	Destabilizing	0.81	D	0.617	neutral	N	0.451603236	None	None	N
Y/P	0.9787	likely_pathogenic	0.9745	pathogenic	-1.669	Destabilizing	0.92	D	0.618	neutral	None	None	None	None	N
Y/Q	0.3074	likely_benign	0.3014	benign	-1.588	Destabilizing	0.739	D	0.599	neutral	None	None	None	None	N
Y/R	0.2809	likely_benign	0.2918	benign	-0.906	Destabilizing	0.85	D	0.628	neutral	None	None	None	None	N
Y/S	0.1642	likely_benign	0.1524	benign	-2.281	Highly Destabilizing	0.549	D	0.569	neutral	N	0.4324974	None	None	N
Y/T	0.2504	likely_benign	0.243	benign	-2.039	Highly Destabilizing	0.617	D	0.602	neutral	None	None	None	None	N
Y/V	0.152	likely_benign	0.1525	benign	-1.669	Destabilizing	0.447	N	0.481	neutral	None	None	None	None	N
Y/W	0.2856	likely_benign	0.2952	benign	-0.147	Destabilizing	0.972	D	0.523	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.