TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28833	86722;86723;86724	chr2:178559635;178559634;178559633	chr2:179424362;179424361;179424360
N2AB	27192	81799;81800;81801	chr2:178559635;178559634;178559633	chr2:179424362;179424361;179424360
N2A	26265	79018;79019;79020	chr2:178559635;178559634;178559633	chr2:179424362;179424361;179424360
N2B	19768	59527;59528;59529	chr2:178559635;178559634;178559633	chr2:179424362;179424361;179424360
Novex-1	19893	59902;59903;59904	chr2:178559635;178559634;178559633	chr2:179424362;179424361;179424360
Novex-2	19960	60103;60104;60105	chr2:178559635;178559634;178559633	chr2:179424362;179424361;179424360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-144
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.4558
• Predicted PPI site: I

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
A/G	None	None	0.166	N	0.353	0.165	0.284539287134	gnomAD-4.0.0	6.84236E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15961E-05	0
A/S	rs368023553	-0.082	0.005	N	0.167	0.084	None	gnomAD-2.1.1	5.36E-05	None	None	None	None	I	None	6.20091E-04	0	None	0	0	None	0	None	0	0	0
A/S	rs368023553	-0.082	0.005	N	0.167	0.084	None	gnomAD-3.1.2	1.57712E-04	None	None	None	None	I	None	5.54778E-04	6.55E-05	0	0	0	None	0	0	0	0	0
A/S	rs368023553	-0.082	0.005	N	0.167	0.084	None	gnomAD-4.0.0	2.60281E-05	None	None	None	None	I	None	5.205E-04	1.66722E-05	None	0	0	None	0	0	0	0	3.20246E-05
A/T	rs368023553	-0.143	0.002	N	0.165	0.093	0.152612264143	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
A/T	rs368023553	-0.143	0.002	N	0.165	0.093	0.152612264143	gnomAD-4.0.0	6.84245E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99499E-07	0	0
A/V	rs374108922	0.007	0.166	N	0.307	0.155	None	gnomAD-2.1.1	5.36E-05	None	None	None	None	I	None	6.20091E-04	0	None	0	0	None	0	None	0	0	0
A/V	rs374108922	0.007	0.166	N	0.307	0.155	None	gnomAD-3.1.2	1.57698E-04	None	None	None	None	I	None	5.54778E-04	6.55E-05	0	0	0	None	0	0	0	0	0
A/V	rs374108922	0.007	0.166	N	0.307	0.155	None	gnomAD-4.0.0	2.60276E-05	None	None	None	None	I	None	5.20486E-04	1.66683E-05	None	0	0	None	0	0	0	0	3.20225E-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
A/C	0.348	ambiguous	0.3505	ambiguous	-0.684	Destabilizing	0.965	D	0.419	neutral	None	None	None	None	I
A/D	0.2473	likely_benign	0.2315	benign	-0.418	Destabilizing	0.491	N	0.576	neutral	N	0.46046594	None	None	I
A/E	0.1961	likely_benign	0.1852	benign	-0.582	Destabilizing	0.561	D	0.455	neutral	None	None	None	None	I
A/F	0.2682	likely_benign	0.2712	benign	-0.903	Destabilizing	0.901	D	0.62	neutral	None	None	None	None	I
A/G	0.1385	likely_benign	0.135	benign	-0.175	Destabilizing	0.166	N	0.353	neutral	N	0.485497671	None	None	I
A/H	0.3303	likely_benign	0.3238	benign	-0.291	Destabilizing	0.901	D	0.591	neutral	None	None	None	None	I
A/I	0.1646	likely_benign	0.1676	benign	-0.315	Destabilizing	0.561	D	0.491	neutral	None	None	None	None	I
A/K	0.2823	likely_benign	0.2744	benign	-0.432	Destabilizing	0.209	N	0.453	neutral	None	None	None	None	I
A/L	0.1457	likely_benign	0.1469	benign	-0.315	Destabilizing	0.209	N	0.45	neutral	None	None	None	None	I
A/M	0.1485	likely_benign	0.1512	benign	-0.332	Destabilizing	0.965	D	0.485	neutral	None	None	None	None	I
A/N	0.1679	likely_benign	0.1683	benign	-0.126	Destabilizing	0.561	D	0.583	neutral	None	None	None	None	I
A/P	0.3099	likely_benign	0.2713	benign	-0.233	Destabilizing	0.662	D	0.495	neutral	N	0.475070033	None	None	I
A/Q	0.249	likely_benign	0.244	benign	-0.421	Destabilizing	0.818	D	0.496	neutral	None	None	None	None	I
A/R	0.2888	likely_benign	0.2803	benign	-0.009	Destabilizing	0.004	N	0.311	neutral	None	None	None	None	I
A/S	0.079	likely_benign	0.0793	benign	-0.29	Destabilizing	0.005	N	0.167	neutral	N	0.35429848	None	None	I
A/T	0.0613	likely_benign	0.0633	benign	-0.381	Destabilizing	0.002	N	0.165	neutral	N	0.362072602	None	None	I
A/V	0.097	likely_benign	0.0989	benign	-0.233	Destabilizing	0.166	N	0.307	neutral	N	0.451827814	None	None	I
A/W	0.6622	likely_pathogenic	0.6521	pathogenic	-1.032	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	I
A/Y	0.3641	ambiguous	0.3559	ambiguous	-0.672	Destabilizing	0.965	D	0.611	neutral	None	None	None	None	I

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.