TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4843	14752;14753;14754	chr2:178735919;178735918;178735917	chr2:179600646;179600645;179600644
N2AB	4526	13801;13802;13803	chr2:178735919;178735918;178735917	chr2:179600646;179600645;179600644
N2A	3599	11020;11021;11022	chr2:178735919;178735918;178735917	chr2:179600646;179600645;179600644
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-31
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3637
• 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
I/T	rs1401764178	-2.07	0.062	N	0.501	0.379	0.663598450264	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
I/T	rs1401764178	-2.07	0.062	N	0.501	0.379	0.663598450264	gnomAD-4.0.0	4.77327E-06	None	None	None	None	N	None	0	6.85965E-05	None	0	0	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
I/A	0.5177	ambiguous	0.4173	ambiguous	-1.966	Destabilizing	0.035	N	0.427	neutral	None	None	None	None	N
I/C	0.6908	likely_pathogenic	0.6278	pathogenic	-0.999	Destabilizing	0.824	D	0.569	neutral	None	None	None	None	N
I/D	0.7679	likely_pathogenic	0.6912	pathogenic	-1.63	Destabilizing	0.081	N	0.603	neutral	None	None	None	None	N
I/E	0.6247	likely_pathogenic	0.5501	ambiguous	-1.556	Destabilizing	0.002	N	0.443	neutral	None	None	None	None	N
I/F	0.1486	likely_benign	0.1222	benign	-1.298	Destabilizing	0.317	N	0.527	neutral	N	0.402503794	None	None	N
I/G	0.7106	likely_pathogenic	0.6239	pathogenic	-2.359	Highly Destabilizing	0.262	N	0.605	neutral	None	None	None	None	N
I/H	0.5201	ambiguous	0.4341	ambiguous	-1.592	Destabilizing	0.935	D	0.601	neutral	None	None	None	None	N
I/K	0.3995	ambiguous	0.3222	benign	-1.368	Destabilizing	0.149	N	0.605	neutral	None	None	None	None	N
I/L	0.1372	likely_benign	0.1139	benign	-0.909	Destabilizing	0.004	N	0.235	neutral	N	0.471739989	None	None	N
I/M	0.1368	likely_benign	0.1155	benign	-0.643	Destabilizing	0.005	N	0.165	neutral	N	0.493137865	None	None	N
I/N	0.3179	likely_benign	0.2494	benign	-1.248	Destabilizing	0.484	N	0.627	neutral	D	0.552865504	None	None	N
I/P	0.7689	likely_pathogenic	0.7077	pathogenic	-1.234	Destabilizing	0.791	D	0.629	neutral	None	None	None	None	N
I/Q	0.4664	ambiguous	0.3853	ambiguous	-1.339	Destabilizing	0.38	N	0.634	neutral	None	None	None	None	N
I/R	0.3368	likely_benign	0.2665	benign	-0.851	Destabilizing	0.38	N	0.635	neutral	None	None	None	None	N
I/S	0.4075	ambiguous	0.3173	benign	-1.859	Destabilizing	0.117	N	0.537	neutral	N	0.51571115	None	None	N
I/T	0.4064	ambiguous	0.3259	benign	-1.659	Destabilizing	0.062	N	0.501	neutral	N	0.507813405	None	None	N
I/V	0.1139	likely_benign	0.1012	benign	-1.234	Destabilizing	None	N	0.133	neutral	N	0.482130136	None	None	N
I/W	0.7317	likely_pathogenic	0.6709	pathogenic	-1.464	Destabilizing	0.935	D	0.627	neutral	None	None	None	None	N
I/Y	0.4321	ambiguous	0.3663	ambiguous	-1.228	Destabilizing	0.555	D	0.59	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.