TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23920	71983;71984;71985	chr2:178574374;178574373;178574372	chr2:179439101;179439100;179439099
N2AB	22279	67060;67061;67062	chr2:178574374;178574373;178574372	chr2:179439101;179439100;179439099
N2A	21352	64279;64280;64281	chr2:178574374;178574373;178574372	chr2:179439101;179439100;179439099
N2B	14855	44788;44789;44790	chr2:178574374;178574373;178574372	chr2:179439101;179439100;179439099
Novex-1	14980	45163;45164;45165	chr2:178574374;178574373;178574372	chr2:179439101;179439100;179439099
Novex-2	15047	45364;45365;45366	chr2:178574374;178574373;178574372	chr2:179439101;179439100;179439099
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-61
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.6368
• 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
L/S	None	None	None	N	0.441	0.153	0.474168873855	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85902E-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
L/A	0.1843	likely_benign	0.2333	benign	-1.255	Destabilizing	0.007	N	0.424	neutral	None	None	None	None	N
L/C	0.2851	likely_benign	0.3714	ambiguous	-0.692	Destabilizing	0.747	D	0.363	neutral	None	None	None	None	N
L/D	0.561	ambiguous	0.6255	pathogenic	-0.745	Destabilizing	0.035	N	0.522	neutral	None	None	None	None	N
L/E	0.3983	ambiguous	0.4311	ambiguous	-0.774	Destabilizing	0.035	N	0.517	neutral	None	None	None	None	N
L/F	0.0543	likely_benign	0.0708	benign	-0.92	Destabilizing	None	N	0.073	neutral	N	0.489964049	None	None	N
L/G	0.4315	ambiguous	0.5182	ambiguous	-1.526	Destabilizing	0.018	N	0.457	neutral	None	None	None	None	N
L/H	0.1921	likely_benign	0.22	benign	-0.676	Destabilizing	0.112	N	0.412	neutral	None	None	None	None	N
L/I	0.0759	likely_benign	0.0905	benign	-0.608	Destabilizing	0.007	N	0.335	neutral	None	None	None	None	N
L/K	0.3445	ambiguous	0.3527	ambiguous	-0.838	Destabilizing	0.018	N	0.471	neutral	None	None	None	None	N
L/M	0.1009	likely_benign	0.1181	benign	-0.475	Destabilizing	0.162	N	0.412	neutral	N	0.494985867	None	None	N
L/N	0.2813	likely_benign	0.3283	benign	-0.636	Destabilizing	0.06	N	0.513	neutral	None	None	None	None	N
L/P	0.1655	likely_benign	0.1828	benign	-0.791	Destabilizing	0.204	N	0.455	neutral	None	None	None	None	N
L/Q	0.1806	likely_benign	0.2021	benign	-0.83	Destabilizing	0.112	N	0.49	neutral	None	None	None	None	N
L/R	0.2364	likely_benign	0.2448	benign	-0.21	Destabilizing	0.112	N	0.476	neutral	None	None	None	None	N
L/S	0.2465	likely_benign	0.3243	benign	-1.167	Destabilizing	None	N	0.441	neutral	N	0.505413504	None	None	N
L/T	0.1697	likely_benign	0.2069	benign	-1.082	Destabilizing	0.018	N	0.425	neutral	None	None	None	None	N
L/V	0.0727	likely_benign	0.0864	benign	-0.791	Destabilizing	0.006	N	0.373	neutral	N	0.455715402	None	None	N
L/W	0.1535	likely_benign	0.1886	benign	-0.975	Destabilizing	0.162	N	0.372	neutral	N	0.490545769	None	None	N
L/Y	0.123	likely_benign	0.1574	benign	-0.75	Destabilizing	None	N	0.189	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.