TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6718	20377;20378;20379	chr2:178727213;178727212;178727211	chr2:179591940;179591939;179591938
N2AB	6401	19426;19427;19428	chr2:178727213;178727212;178727211	chr2:179591940;179591939;179591938
N2A	5474	16645;16646;16647	chr2:178727213;178727212;178727211	chr2:179591940;179591939;179591938
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-51
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.3154
• 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
F/L	None	None	0.92	N	0.575	0.284	0.662550749481	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
F/A	0.8997	likely_pathogenic	0.8853	pathogenic	-1.907	Destabilizing	0.973	D	0.715	prob.delet.	None	None	None	None	N
F/C	0.8331	likely_pathogenic	0.7596	pathogenic	-1.095	Destabilizing	1.0	D	0.785	deleterious	N	0.509988783	None	None	N
F/D	0.9668	likely_pathogenic	0.9658	pathogenic	-0.175	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
F/E	0.9692	likely_pathogenic	0.9659	pathogenic	-0.07	Destabilizing	0.995	D	0.777	deleterious	None	None	None	None	N
F/G	0.9606	likely_pathogenic	0.9555	pathogenic	-2.247	Highly Destabilizing	0.994	D	0.762	deleterious	None	None	None	None	N
F/H	0.8636	likely_pathogenic	0.8511	pathogenic	-0.526	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
F/I	0.5411	ambiguous	0.4995	ambiguous	-0.898	Destabilizing	0.965	D	0.6	neutral	D	0.533827548	None	None	N
F/K	0.9712	likely_pathogenic	0.9694	pathogenic	-1.015	Destabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
F/L	0.9396	likely_pathogenic	0.9392	pathogenic	-0.898	Destabilizing	0.92	D	0.575	neutral	N	0.517492659	None	None	N
F/M	0.7555	likely_pathogenic	0.7438	pathogenic	-0.735	Destabilizing	0.98	D	0.669	neutral	None	None	None	None	N
F/N	0.9076	likely_pathogenic	0.9008	pathogenic	-1.106	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
F/P	0.998	likely_pathogenic	0.9979	pathogenic	-1.226	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
F/Q	0.9501	likely_pathogenic	0.9425	pathogenic	-1.092	Destabilizing	0.997	D	0.801	deleterious	None	None	None	None	N
F/R	0.9334	likely_pathogenic	0.9296	pathogenic	-0.496	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
F/S	0.8136	likely_pathogenic	0.7979	pathogenic	-1.98	Destabilizing	0.839	D	0.553	neutral	D	0.526130785	None	None	N
F/T	0.8769	likely_pathogenic	0.8628	pathogenic	-1.78	Destabilizing	0.994	D	0.766	deleterious	None	None	None	None	N
F/V	0.5077	ambiguous	0.4552	ambiguous	-1.226	Destabilizing	0.35	N	0.487	neutral	N	0.501656415	None	None	N
F/W	0.7323	likely_pathogenic	0.7026	pathogenic	0.01	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
F/Y	0.3359	likely_benign	0.3039	benign	-0.227	Destabilizing	0.994	D	0.623	neutral	N	0.519666172	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.