TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31119	93580;93581;93582	chr2:178548271;178548270;178548269	chr2:179412998;179412997;179412996
N2AB	29478	88657;88658;88659	chr2:178548271;178548270;178548269	chr2:179412998;179412997;179412996
N2A	28551	85876;85877;85878	chr2:178548271;178548270;178548269	chr2:179412998;179412997;179412996
N2B	22054	66385;66386;66387	chr2:178548271;178548270;178548269	chr2:179412998;179412997;179412996
Novex-1	22179	66760;66761;66762	chr2:178548271;178548270;178548269	chr2:179412998;179412997;179412996
Novex-2	22246	66961;66962;66963	chr2:178548271;178548270;178548269	chr2:179412998;179412997;179412996
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: Fn3-115
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.3967
• 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/K	None	None	0.997	N	0.511	0.329	0.295623431141	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	0.7551	likely_pathogenic	0.6453	pathogenic	-0.07	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	N
R/C	0.4193	ambiguous	0.3136	benign	-0.097	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
R/D	0.8844	likely_pathogenic	0.8208	pathogenic	0.057	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
R/E	0.7035	likely_pathogenic	0.5813	pathogenic	0.152	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/F	0.8186	likely_pathogenic	0.7128	pathogenic	-0.123	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/G	0.6105	likely_pathogenic	0.4692	ambiguous	-0.325	Destabilizing	1.0	D	0.681	prob.neutral	N	0.432302612	None	None	N
R/H	0.203	likely_benign	0.1538	benign	-0.848	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/I	0.6	likely_pathogenic	0.4641	ambiguous	0.58	Stabilizing	1.0	D	0.765	deleterious	N	0.488985401	None	None	N
R/K	0.1978	likely_benign	0.1661	benign	-0.08	Destabilizing	0.997	D	0.511	neutral	N	0.383319373	None	None	N
R/L	0.5176	ambiguous	0.396	ambiguous	0.58	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
R/M	0.5686	likely_pathogenic	0.4205	ambiguous	0.109	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
R/N	0.7964	likely_pathogenic	0.6928	pathogenic	0.236	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/P	0.9171	likely_pathogenic	0.8891	pathogenic	0.386	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/Q	0.1837	likely_benign	0.1423	benign	0.142	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
R/S	0.7837	likely_pathogenic	0.6689	pathogenic	-0.215	Destabilizing	1.0	D	0.723	prob.delet.	N	0.411140693	None	None	N
R/T	0.5984	likely_pathogenic	0.4403	ambiguous	0.04	Stabilizing	1.0	D	0.712	prob.delet.	N	0.450467085	None	None	N
R/V	0.6851	likely_pathogenic	0.5601	ambiguous	0.386	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/W	0.4138	ambiguous	0.2934	benign	-0.07	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
R/Y	0.6227	likely_pathogenic	0.4964	ambiguous	0.315	Stabilizing	1.0	D	0.767	deleterious	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.