TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33220	99883;99884;99885	chr2:178537549;178537548;178537547	chr2:179402276;179402275;179402274
N2AB	31579	94960;94961;94962	chr2:178537549;178537548;178537547	chr2:179402276;179402275;179402274
N2A	30652	92179;92180;92181	chr2:178537549;178537548;178537547	chr2:179402276;179402275;179402274
N2B	24155	72688;72689;72690	chr2:178537549;178537548;178537547	chr2:179402276;179402275;179402274
Novex-1	24280	73063;73064;73065	chr2:178537549;178537548;178537547	chr2:179402276;179402275;179402274
Novex-2	24347	73264;73265;73266	chr2:178537549;178537548;178537547	chr2:179402276;179402275;179402274
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-157
• Domain position: 18
• Structural Position: 35
• Q(SASA): 0.08
• 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
Y/C	None	None	1.0	N	0.697	0.558	0.61844985043	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
Y/H	rs776277442	-3.152	1.0	N	0.747	0.55	0.504175077286	gnomAD-4.0.0	1.11401E-05	None	None	None	None	N	None	0	0	None	0	1.94175E-04	None	0	0	0	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
Y/A	0.9692	likely_pathogenic	0.9714	pathogenic	-3.029	Highly Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
Y/C	0.6484	likely_pathogenic	0.7136	pathogenic	-1.488	Destabilizing	1.0	D	0.697	prob.neutral	N	0.485857367	None	None	N
Y/D	0.9927	likely_pathogenic	0.9934	pathogenic	-2.842	Highly Destabilizing	1.0	D	0.747	deleterious	N	0.485857367	None	None	N
Y/E	0.9975	likely_pathogenic	0.9977	pathogenic	-2.695	Highly Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
Y/F	0.18	likely_benign	0.2075	benign	-1.182	Destabilizing	1.0	D	0.511	neutral	N	0.472893733	None	None	N
Y/G	0.9579	likely_pathogenic	0.9578	pathogenic	-3.394	Highly Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
Y/H	0.8997	likely_pathogenic	0.898	pathogenic	-1.829	Destabilizing	1.0	D	0.747	deleterious	N	0.485857367	None	None	N
Y/I	0.925	likely_pathogenic	0.9439	pathogenic	-1.841	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
Y/K	0.9955	likely_pathogenic	0.9949	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
Y/L	0.8757	likely_pathogenic	0.9162	pathogenic	-1.841	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
Y/M	0.9568	likely_pathogenic	0.9642	pathogenic	-1.368	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
Y/N	0.9408	likely_pathogenic	0.9428	pathogenic	-2.596	Highly Destabilizing	1.0	D	0.717	prob.delet.	N	0.485857367	None	None	N
Y/P	0.9953	likely_pathogenic	0.9955	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
Y/Q	0.9929	likely_pathogenic	0.9933	pathogenic	-2.468	Highly Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
Y/R	0.9844	likely_pathogenic	0.9838	pathogenic	-1.601	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
Y/S	0.9379	likely_pathogenic	0.94	pathogenic	-2.971	Highly Destabilizing	1.0	D	0.705	prob.neutral	D	0.523610555	None	None	N
Y/T	0.9755	likely_pathogenic	0.9762	pathogenic	-2.727	Highly Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
Y/V	0.8156	likely_pathogenic	0.855	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
Y/W	0.8073	likely_pathogenic	0.8122	pathogenic	-0.63	Destabilizing	1.0	D	0.749	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.