TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30302	91129;91130;91131	chr2:178551996;178551995;178551994	chr2:179416723;179416722;179416721
N2AB	28661	86206;86207;86208	chr2:178551996;178551995;178551994	chr2:179416723;179416722;179416721
N2A	27734	83425;83426;83427	chr2:178551996;178551995;178551994	chr2:179416723;179416722;179416721
N2B	21237	63934;63935;63936	chr2:178551996;178551995;178551994	chr2:179416723;179416722;179416721
Novex-1	21362	64309;64310;64311	chr2:178551996;178551995;178551994	chr2:179416723;179416722;179416721
Novex-2	21429	64510;64511;64512	chr2:178551996;178551995;178551994	chr2:179416723;179416722;179416721
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-108
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.4288
• 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
E/K	rs1553538924	None	0.999	N	0.591	0.363	0.362758974969	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
E/A	0.7019	likely_pathogenic	0.7011	pathogenic	-0.385	Destabilizing	0.999	D	0.721	prob.delet.	N	0.481849263	None	None	N
E/C	0.9785	likely_pathogenic	0.9775	pathogenic	-0.233	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/D	0.8615	likely_pathogenic	0.8739	pathogenic	-1.152	Destabilizing	0.999	D	0.441	neutral	D	0.537367023	None	None	N
E/F	0.9873	likely_pathogenic	0.9868	pathogenic	-0.868	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
E/G	0.7994	likely_pathogenic	0.8134	pathogenic	-0.661	Destabilizing	1.0	D	0.791	deleterious	N	0.514654412	None	None	N
E/H	0.9562	likely_pathogenic	0.9503	pathogenic	-1.143	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/I	0.868	likely_pathogenic	0.8647	pathogenic	0.33	Stabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
E/K	0.7125	likely_pathogenic	0.7052	pathogenic	-0.284	Destabilizing	0.999	D	0.591	neutral	N	0.482863221	None	None	N
E/L	0.9507	likely_pathogenic	0.9459	pathogenic	0.33	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/M	0.901	likely_pathogenic	0.8955	pathogenic	0.741	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/N	0.9305	likely_pathogenic	0.9326	pathogenic	-0.495	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/P	0.999	likely_pathogenic	0.9989	pathogenic	0.114	Stabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
E/Q	0.4084	ambiguous	0.3798	ambiguous	-0.43	Destabilizing	1.0	D	0.651	neutral	N	0.472556872	None	None	N
E/R	0.8263	likely_pathogenic	0.8118	pathogenic	-0.405	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/S	0.7911	likely_pathogenic	0.7929	pathogenic	-0.823	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/T	0.8258	likely_pathogenic	0.8238	pathogenic	-0.582	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/V	0.7139	likely_pathogenic	0.7003	pathogenic	0.114	Stabilizing	1.0	D	0.847	deleterious	N	0.500559471	None	None	N
E/W	0.9954	likely_pathogenic	0.9955	pathogenic	-1.044	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/Y	0.9836	likely_pathogenic	0.9824	pathogenic	-0.676	Destabilizing	1.0	D	0.862	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.