TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25770	77533;77534;77535	chr2:178568824;178568823;178568822	chr2:179433551;179433550;179433549
N2AB	24129	72610;72611;72612	chr2:178568824;178568823;178568822	chr2:179433551;179433550;179433549
N2A	23202	69829;69830;69831	chr2:178568824;178568823;178568822	chr2:179433551;179433550;179433549
N2B	16705	50338;50339;50340	chr2:178568824;178568823;178568822	chr2:179433551;179433550;179433549
Novex-1	16830	50713;50714;50715	chr2:178568824;178568823;178568822	chr2:179433551;179433550;179433549
Novex-2	16897	50914;50915;50916	chr2:178568824;178568823;178568822	chr2:179433551;179433550;179433549
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: Fn3-75
• Domain position: 73
• Structural Position: 107
• Q(SASA): 0.1554
• 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/S	None	None	0.999	N	0.569	0.517	0.491729458163	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.965	likely_pathogenic	0.9524	pathogenic	-1.725	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	N
R/C	0.5513	ambiguous	0.5095	ambiguous	-1.642	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
R/D	0.9961	likely_pathogenic	0.9948	pathogenic	-0.83	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
R/E	0.9417	likely_pathogenic	0.9224	pathogenic	-0.62	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	N
R/F	0.9892	likely_pathogenic	0.9863	pathogenic	-0.92	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
R/G	0.9583	likely_pathogenic	0.9392	pathogenic	-2.065	Highly Destabilizing	0.999	D	0.594	neutral	D	0.55332582	None	None	N
R/H	0.3639	ambiguous	0.3463	ambiguous	-1.93	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
R/I	0.952	likely_pathogenic	0.9461	pathogenic	-0.744	Destabilizing	1.0	D	0.725	prob.delet.	N	0.51234437	None	None	N
R/K	0.4885	ambiguous	0.4319	ambiguous	-1.148	Destabilizing	0.533	D	0.322	neutral	N	0.488982968	None	None	N
R/L	0.919	likely_pathogenic	0.9048	pathogenic	-0.744	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
R/M	0.9491	likely_pathogenic	0.9272	pathogenic	-1.287	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
R/N	0.9803	likely_pathogenic	0.9744	pathogenic	-1.124	Destabilizing	1.0	D	0.541	neutral	None	None	None	None	N
R/P	0.9992	likely_pathogenic	0.9989	pathogenic	-1.059	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
R/Q	0.3205	likely_benign	0.2657	benign	-0.969	Destabilizing	1.0	D	0.536	neutral	None	None	None	None	N
R/S	0.9658	likely_pathogenic	0.9527	pathogenic	-1.953	Destabilizing	0.999	D	0.569	neutral	N	0.503453146	None	None	N
R/T	0.9501	likely_pathogenic	0.9247	pathogenic	-1.54	Destabilizing	1.0	D	0.584	neutral	N	0.495326071	None	None	N
R/V	0.9539	likely_pathogenic	0.9435	pathogenic	-1.059	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
R/W	0.8218	likely_pathogenic	0.7973	pathogenic	-0.501	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
R/Y	0.9519	likely_pathogenic	0.9426	pathogenic	-0.331	Destabilizing	1.0	D	0.707	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.