TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25835	77728;77729;77730	chr2:178568629;178568628;178568627	chr2:179433356;179433355;179433354
N2AB	24194	72805;72806;72807	chr2:178568629;178568628;178568627	chr2:179433356;179433355;179433354
N2A	23267	70024;70025;70026	chr2:178568629;178568628;178568627	chr2:179433356;179433355;179433354
N2B	16770	50533;50534;50535	chr2:178568629;178568628;178568627	chr2:179433356;179433355;179433354
Novex-1	16895	50908;50909;50910	chr2:178568629;178568628;178568627	chr2:179433356;179433355;179433354
Novex-2	16962	51109;51110;51111	chr2:178568629;178568628;178568627	chr2:179433356;179433355;179433354
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-136
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.4379
• 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
G/D	None	None	0.004	N	0.297	0.107	0.0884992946249	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85994E-06	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
G/A	0.1749	likely_benign	0.1835	benign	-0.22	Destabilizing	0.007	N	0.313	neutral	N	0.505460473	None	None	N
G/C	0.1963	likely_benign	0.2123	benign	-0.91	Destabilizing	0.976	D	0.711	prob.delet.	D	0.544328782	None	None	N
G/D	0.1291	likely_benign	0.1397	benign	-0.537	Destabilizing	0.004	N	0.297	neutral	N	0.516667861	None	None	N
G/E	0.1887	likely_benign	0.1918	benign	-0.701	Destabilizing	0.539	D	0.571	neutral	None	None	None	None	N
G/F	0.499	ambiguous	0.5303	ambiguous	-0.974	Destabilizing	0.947	D	0.701	prob.neutral	None	None	None	None	N
G/H	0.2507	likely_benign	0.2687	benign	-0.385	Destabilizing	0.947	D	0.633	neutral	None	None	None	None	N
G/I	0.3267	likely_benign	0.3626	ambiguous	-0.424	Destabilizing	0.826	D	0.71	prob.delet.	None	None	None	None	N
G/K	0.2963	likely_benign	0.2983	benign	-0.719	Destabilizing	0.7	D	0.617	neutral	None	None	None	None	N
G/L	0.4084	ambiguous	0.4218	ambiguous	-0.424	Destabilizing	0.7	D	0.689	prob.neutral	None	None	None	None	N
G/M	0.4163	ambiguous	0.4294	ambiguous	-0.518	Destabilizing	0.982	D	0.701	prob.neutral	None	None	None	None	N
G/N	0.1397	likely_benign	0.139	benign	-0.41	Destabilizing	0.539	D	0.593	neutral	None	None	None	None	N
G/P	0.9163	likely_pathogenic	0.9316	pathogenic	-0.326	Destabilizing	0.826	D	0.617	neutral	None	None	None	None	N
G/Q	0.2254	likely_benign	0.2286	benign	-0.685	Destabilizing	0.7	D	0.637	neutral	None	None	None	None	N
G/R	0.2306	likely_benign	0.2394	benign	-0.277	Destabilizing	0.638	D	0.633	neutral	N	0.507017409	None	None	N
G/S	0.0995	likely_benign	0.1031	benign	-0.548	Destabilizing	0.015	N	0.297	neutral	N	0.499660348	None	None	N
G/T	0.1968	likely_benign	0.2044	benign	-0.642	Destabilizing	0.539	D	0.567	neutral	None	None	None	None	N
G/V	0.2669	likely_benign	0.2992	benign	-0.326	Destabilizing	0.638	D	0.691	prob.neutral	D	0.544328782	None	None	N
G/W	0.435	ambiguous	0.4665	ambiguous	-1.108	Destabilizing	0.982	D	0.653	neutral	None	None	None	None	N
G/Y	0.341	ambiguous	0.3653	ambiguous	-0.772	Destabilizing	0.982	D	0.71	prob.delet.	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.