TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15623	47092;47093;47094	chr2:178618683;178618682;178618681	chr2:179483410;179483409;179483408
N2AB	13982	42169;42170;42171	chr2:178618683;178618682;178618681	chr2:179483410;179483409;179483408
N2A	13055	39388;39389;39390	chr2:178618683;178618682;178618681	chr2:179483410;179483409;179483408
N2B	6558	19897;19898;19899	chr2:178618683;178618682;178618681	chr2:179483410;179483409;179483408
Novex-1	6683	20272;20273;20274	chr2:178618683;178618682;178618681	chr2:179483410;179483409;179483408
Novex-2	6750	20473;20474;20475	chr2:178618683;178618682;178618681	chr2:179483410;179483409;179483408
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-108
• Domain position: 56
• Structural Position: 139
• Q(SASA): 0.3646
• 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
R/G	None	None	0.939	N	0.616	0.419	0.423119698836	gnomAD-4.0.0	1.5947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.864E-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
R/A	0.2939	likely_benign	0.3877	ambiguous	-0.526	Destabilizing	0.953	D	0.557	neutral	None	None	None	None	N
R/C	0.1565	likely_benign	0.1885	benign	-0.561	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/D	0.5324	ambiguous	0.6415	pathogenic	0.142	Stabilizing	0.986	D	0.695	prob.neutral	None	None	None	None	N
R/E	0.2581	likely_benign	0.3459	ambiguous	0.259	Stabilizing	0.91	D	0.475	neutral	None	None	None	None	N
R/F	0.4187	ambiguous	0.543	ambiguous	-0.457	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
R/G	0.2464	likely_benign	0.324	benign	-0.81	Destabilizing	0.939	D	0.616	neutral	N	0.516834958	None	None	N
R/H	0.09	likely_benign	0.1001	benign	-1.137	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
R/I	0.18	likely_benign	0.222	benign	0.22	Stabilizing	0.991	D	0.695	prob.neutral	N	0.512649789	None	None	N
R/K	0.078	likely_benign	0.0995	benign	-0.446	Destabilizing	0.046	N	0.263	neutral	N	0.494652956	None	None	N
R/L	0.1952	likely_benign	0.2541	benign	0.22	Stabilizing	0.953	D	0.616	neutral	None	None	None	None	N
R/M	0.2023	likely_benign	0.2623	benign	-0.211	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
R/N	0.3701	ambiguous	0.4706	ambiguous	-0.057	Destabilizing	0.986	D	0.593	neutral	None	None	None	None	N
R/P	0.7035	likely_pathogenic	0.8017	pathogenic	-0.007	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
R/Q	0.0864	likely_benign	0.0993	benign	-0.188	Destabilizing	0.986	D	0.596	neutral	None	None	None	None	N
R/S	0.3095	likely_benign	0.4021	ambiguous	-0.753	Destabilizing	0.939	D	0.635	neutral	N	0.514543533	None	None	N
R/T	0.1377	likely_benign	0.1738	benign	-0.458	Destabilizing	0.982	D	0.694	prob.neutral	N	0.505375636	None	None	N
R/V	0.2276	likely_benign	0.285	benign	-0.007	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
R/W	0.1698	likely_benign	0.2276	benign	-0.221	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
R/Y	0.2953	likely_benign	0.4062	ambiguous	0.108	Stabilizing	0.998	D	0.698	prob.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.