TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4927	15004;15005;15006	chr2:178735667;178735666;178735665	chr2:179600394;179600393;179600392
N2AB	4610	14053;14054;14055	chr2:178735667;178735666;178735665	chr2:179600394;179600393;179600392
N2A	3683	11272;11273;11274	chr2:178735667;178735666;178735665	chr2:179600394;179600393;179600392
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-32
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.5177
• 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
K/N	rs780599464	0.2	0.007	N	0.291	0.129	0.126345400529	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	2.9E-05	None	0	5.58E-05	None	0	None	0	0	0
K/N	rs780599464	0.2	0.007	N	0.291	0.129	0.126345400529	gnomAD-4.0.0	6.84233E-07	None	None	None	None	N	None	0	0	None	0	2.52156E-05	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
K/A	0.2364	likely_benign	0.289	benign	0.005	Stabilizing	0.575	D	0.569	neutral	None	None	None	None	N
K/C	0.5477	ambiguous	0.6185	pathogenic	-0.262	Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	N
K/D	0.4007	ambiguous	0.5006	ambiguous	0.168	Stabilizing	0.404	N	0.565	neutral	None	None	None	None	N
K/E	0.1441	likely_benign	0.1845	benign	0.186	Stabilizing	0.013	N	0.329	neutral	N	0.439928017	None	None	N
K/F	0.5055	ambiguous	0.5748	pathogenic	-0.157	Destabilizing	0.967	D	0.691	prob.neutral	None	None	None	None	N
K/G	0.3354	likely_benign	0.3965	ambiguous	-0.207	Destabilizing	0.404	N	0.577	neutral	None	None	None	None	N
K/H	0.2175	likely_benign	0.2463	benign	-0.462	Destabilizing	0.826	D	0.625	neutral	None	None	None	None	N
K/I	0.1692	likely_benign	0.2035	benign	0.487	Stabilizing	0.879	D	0.695	prob.neutral	N	0.514763418	None	None	N
K/L	0.1988	likely_benign	0.2325	benign	0.487	Stabilizing	0.575	D	0.551	neutral	None	None	None	None	N
K/M	0.1422	likely_benign	0.1631	benign	0.202	Stabilizing	0.991	D	0.626	neutral	None	None	None	None	N
K/N	0.2394	likely_benign	0.29	benign	0.17	Stabilizing	0.007	N	0.291	neutral	N	0.514434445	None	None	N
K/P	0.3303	likely_benign	0.3943	ambiguous	0.355	Stabilizing	0.906	D	0.62	neutral	None	None	None	None	N
K/Q	0.1087	likely_benign	0.1226	benign	0.033	Stabilizing	0.505	D	0.553	neutral	N	0.398710167	None	None	N
K/R	0.0797	likely_benign	0.0825	benign	-0.079	Destabilizing	0.007	N	0.299	neutral	N	0.504000445	None	None	N
K/S	0.2699	likely_benign	0.3317	benign	-0.332	Destabilizing	0.404	N	0.534	neutral	None	None	None	None	N
K/T	0.1269	likely_benign	0.153	benign	-0.158	Destabilizing	0.338	N	0.551	neutral	N	0.51314631	None	None	N
K/V	0.1818	likely_benign	0.2219	benign	0.355	Stabilizing	0.906	D	0.594	neutral	None	None	None	None	N
K/W	0.5726	likely_pathogenic	0.6277	pathogenic	-0.174	Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	N
K/Y	0.3844	ambiguous	0.4454	ambiguous	0.179	Stabilizing	0.967	D	0.675	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.