TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19334	58225;58226;58227	chr2:178594494;178594493;178594492	chr2:179459221;179459220;179459219
N2AB	17693	53302;53303;53304	chr2:178594494;178594493;178594492	chr2:179459221;179459220;179459219
N2A	16766	50521;50522;50523	chr2:178594494;178594493;178594492	chr2:179459221;179459220;179459219
N2B	10269	31030;31031;31032	chr2:178594494;178594493;178594492	chr2:179459221;179459220;179459219
Novex-1	10394	31405;31406;31407	chr2:178594494;178594493;178594492	chr2:179459221;179459220;179459219
Novex-2	10461	31606;31607;31608	chr2:178594494;178594493;178594492	chr2:179459221;179459220;179459219
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-28
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2136
• 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
V/D	rs546716167	-2.111	0.966	N	0.579	0.433	0.839459519749	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
V/D	rs546716167	-2.111	0.966	N	0.579	0.433	0.839459519749	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.1425E-04	0
V/D	rs546716167	-2.111	0.966	N	0.579	0.433	0.839459519749	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
V/D	rs546716167	-2.111	0.966	N	0.579	0.433	0.839459519749	gnomAD-4.0.0	8.67741E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.42791E-04	1.60087E-05
V/I	None	-0.649	0.801	N	0.459	0.203	0.469496741337	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	1.29232E-04	0	None	0	0	None	0	None	0	0	0
V/I	None	-0.649	0.801	N	0.459	0.203	0.469496741337	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	None	-0.649	0.801	N	0.459	0.203	0.469496741337	gnomAD-4.0.0	2.47943E-06	None	None	None	None	N	None	2.67001E-05	0	None	0	0	None	0	0	0	2.19674E-05	0
V/L	rs769006307	None	0.625	N	0.439	0.217	0.360163838653	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	1.31165E-04	0	0	0	None	0	0	0	0	0
V/L	rs769006307	None	0.625	N	0.439	0.217	0.360163838653	gnomAD-4.0.0	3.09928E-06	None	None	None	None	N	None	0	3.33656E-05	None	0	0	None	0	0	1.69555E-06	0	1.60133E-05

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
V/A	0.3467	ambiguous	0.3202	benign	-1.43	Destabilizing	0.005	N	0.221	neutral	N	0.439135371	None	None	N
V/C	0.8089	likely_pathogenic	0.8076	pathogenic	-1.121	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
V/D	0.8341	likely_pathogenic	0.7478	pathogenic	-1.01	Destabilizing	0.966	D	0.579	neutral	N	0.480941118	None	None	N
V/E	0.6874	likely_pathogenic	0.6025	pathogenic	-0.95	Destabilizing	0.842	D	0.513	neutral	None	None	None	None	N
V/F	0.4409	ambiguous	0.3206	benign	-0.957	Destabilizing	0.989	D	0.523	neutral	N	0.471658273	None	None	N
V/G	0.5768	likely_pathogenic	0.4893	ambiguous	-1.8	Destabilizing	0.002	N	0.474	neutral	N	0.484157122	None	None	N
V/H	0.8765	likely_pathogenic	0.8127	pathogenic	-1.219	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	N
V/I	0.0862	likely_benign	0.0816	benign	-0.495	Destabilizing	0.801	D	0.459	neutral	N	0.468610129	None	None	N
V/K	0.781	likely_pathogenic	0.6948	pathogenic	-1.195	Destabilizing	0.842	D	0.521	neutral	None	None	None	None	N
V/L	0.3109	likely_benign	0.2628	benign	-0.495	Destabilizing	0.625	D	0.439	neutral	N	0.458835852	None	None	N
V/M	0.2912	likely_benign	0.2355	benign	-0.523	Destabilizing	0.991	D	0.476	neutral	None	None	None	None	N
V/N	0.6842	likely_pathogenic	0.5981	pathogenic	-1.149	Destabilizing	0.974	D	0.594	neutral	None	None	None	None	N
V/P	0.914	likely_pathogenic	0.8697	pathogenic	-0.771	Destabilizing	0.974	D	0.577	neutral	None	None	None	None	N
V/Q	0.7215	likely_pathogenic	0.6543	pathogenic	-1.188	Destabilizing	0.974	D	0.587	neutral	None	None	None	None	N
V/R	0.7857	likely_pathogenic	0.7005	pathogenic	-0.792	Destabilizing	0.974	D	0.596	neutral	None	None	None	None	N
V/S	0.5943	likely_pathogenic	0.521	ambiguous	-1.753	Destabilizing	0.728	D	0.505	neutral	None	None	None	None	N
V/T	0.4286	ambiguous	0.3832	ambiguous	-1.555	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	N
V/W	0.9638	likely_pathogenic	0.9338	pathogenic	-1.169	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
V/Y	0.8278	likely_pathogenic	0.7511	pathogenic	-0.848	Destabilizing	0.991	D	0.537	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.