TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23206	69841;69842;69843	chr2:178576628;178576627;178576626	chr2:179441355;179441354;179441353
N2AB	21565	64918;64919;64920	chr2:178576628;178576627;178576626	chr2:179441355;179441354;179441353
N2A	20638	62137;62138;62139	chr2:178576628;178576627;178576626	chr2:179441355;179441354;179441353
N2B	14141	42646;42647;42648	chr2:178576628;178576627;178576626	chr2:179441355;179441354;179441353
Novex-1	14266	43021;43022;43023	chr2:178576628;178576627;178576626	chr2:179441355;179441354;179441353
Novex-2	14333	43222;43223;43224	chr2:178576628;178576627;178576626	chr2:179441355;179441354;179441353
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: Fn3-56
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5957
• 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/Q	rs1244129033	0.27	0.997	N	0.726	0.342	0.367803931526	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/Q	rs1244129033	0.27	0.997	N	0.726	0.342	0.367803931526	gnomAD-4.0.0	2.05282E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69867E-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	0.2121	likely_benign	0.1935	benign	-0.6	Destabilizing	0.977	D	0.651	neutral	D	0.522865901	None	None	N
E/C	0.9313	likely_pathogenic	0.9242	pathogenic	-0.022	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/D	0.2467	likely_benign	0.2346	benign	-0.541	Destabilizing	0.117	N	0.215	neutral	N	0.507376712	None	None	N
E/F	0.924	likely_pathogenic	0.9168	pathogenic	-0.599	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/G	0.3407	ambiguous	0.3493	ambiguous	-0.817	Destabilizing	0.993	D	0.627	neutral	N	0.512403141	None	None	N
E/H	0.7455	likely_pathogenic	0.7386	pathogenic	-0.622	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.5658	likely_pathogenic	0.5287	ambiguous	-0.055	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/K	0.3565	ambiguous	0.357	ambiguous	0.119	Stabilizing	0.977	D	0.658	neutral	N	0.481675133	None	None	N
E/L	0.68	likely_pathogenic	0.6472	pathogenic	-0.055	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
E/M	0.6825	likely_pathogenic	0.6632	pathogenic	0.263	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/N	0.472	ambiguous	0.4471	ambiguous	-0.138	Destabilizing	0.99	D	0.744	deleterious	None	None	None	None	N
E/P	0.4694	ambiguous	0.4016	ambiguous	-0.216	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
E/Q	0.2429	likely_benign	0.2445	benign	-0.125	Destabilizing	0.997	D	0.726	prob.delet.	N	0.473534832	None	None	N
E/R	0.516	ambiguous	0.523	ambiguous	0.229	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.3671	ambiguous	0.343	ambiguous	-0.327	Destabilizing	0.983	D	0.666	neutral	None	None	None	None	N
E/T	0.4038	ambiguous	0.3777	ambiguous	-0.156	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
E/V	0.3523	ambiguous	0.3339	benign	-0.216	Destabilizing	0.997	D	0.669	neutral	N	0.492399555	None	None	N
E/W	0.9732	likely_pathogenic	0.9718	pathogenic	-0.461	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/Y	0.8571	likely_pathogenic	0.8478	pathogenic	-0.363	Destabilizing	1.0	D	0.671	neutral	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.