TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32935	99028;99029;99030	chr2:178539132;178539131;178539130	chr2:179403859;179403858;179403857
N2AB	31294	94105;94106;94107	chr2:178539132;178539131;178539130	chr2:179403859;179403858;179403857
N2A	30367	91324;91325;91326	chr2:178539132;178539131;178539130	chr2:179403859;179403858;179403857
N2B	23870	71833;71834;71835	chr2:178539132;178539131;178539130	chr2:179403859;179403858;179403857
Novex-1	23995	72208;72209;72210	chr2:178539132;178539131;178539130	chr2:179403859;179403858;179403857
Novex-2	24062	72409;72410;72411	chr2:178539132;178539131;178539130	chr2:179403859;179403858;179403857
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: Fn3-128
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.177
• 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/G	rs879037584	None	0.993	D	0.758	0.52	None	gnomAD-4.0.0	3.18265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71713E-06	0	0
E/K	rs1407053984	-1.495	0.996	N	0.653	0.441	0.456368778954	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs1407053984	-1.495	0.996	N	0.653	0.441	0.456368778954	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs1407053984	-1.495	0.996	N	0.653	0.441	0.456368778954	gnomAD-4.0.0	1.11555E-05	None	None	None	None	N	None	2.67144E-05	3.33456E-05	None	0	0	None	0	0	1.01717E-05	2.19568E-05	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	0.9353	likely_pathogenic	0.936	pathogenic	-1.658	Destabilizing	0.977	D	0.678	prob.neutral	D	0.537824777	None	None	N
E/C	0.9934	likely_pathogenic	0.9909	pathogenic	-0.901	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.5407	ambiguous	0.5538	ambiguous	-1.726	Destabilizing	0.117	N	0.299	neutral	N	0.46780084	None	None	N
E/F	0.992	likely_pathogenic	0.9898	pathogenic	-1.281	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/G	0.9637	likely_pathogenic	0.9692	pathogenic	-2.045	Highly Destabilizing	0.993	D	0.758	deleterious	D	0.528242898	None	None	N
E/H	0.9781	likely_pathogenic	0.9748	pathogenic	-1.217	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/I	0.9775	likely_pathogenic	0.9751	pathogenic	-0.541	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
E/K	0.9663	likely_pathogenic	0.9657	pathogenic	-1.74	Destabilizing	0.996	D	0.653	neutral	N	0.518453074	None	None	N
E/L	0.9703	likely_pathogenic	0.9677	pathogenic	-0.541	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
E/M	0.9787	likely_pathogenic	0.9743	pathogenic	0.192	Stabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/N	0.9687	likely_pathogenic	0.9629	pathogenic	-1.91	Destabilizing	0.99	D	0.777	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9997	pathogenic	-0.901	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
E/Q	0.7817	likely_pathogenic	0.7611	pathogenic	-1.622	Destabilizing	0.999	D	0.749	deleterious	N	0.506301725	None	None	N
E/R	0.9713	likely_pathogenic	0.9733	pathogenic	-1.525	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
E/S	0.9279	likely_pathogenic	0.9248	pathogenic	-2.564	Highly Destabilizing	0.983	D	0.662	neutral	None	None	None	None	N
E/T	0.972	likely_pathogenic	0.9701	pathogenic	-2.202	Highly Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
E/V	0.9493	likely_pathogenic	0.9446	pathogenic	-0.901	Destabilizing	0.997	D	0.809	deleterious	N	0.509124685	None	None	N
E/W	0.9951	likely_pathogenic	0.9949	pathogenic	-1.35	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/Y	0.9851	likely_pathogenic	0.9809	pathogenic	-1.115	Destabilizing	1.0	D	0.844	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.