TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33060	99403;99404;99405	chr2:178538651;178538650;178538649	chr2:179403378;179403377;179403376
N2AB	31419	94480;94481;94482	chr2:178538651;178538650;178538649	chr2:179403378;179403377;179403376
N2A	30492	91699;91700;91701	chr2:178538651;178538650;178538649	chr2:179403378;179403377;179403376
N2B	23995	72208;72209;72210	chr2:178538651;178538650;178538649	chr2:179403378;179403377;179403376
Novex-1	24120	72583;72584;72585	chr2:178538651;178538650;178538649	chr2:179403378;179403377;179403376
Novex-2	24187	72784;72785;72786	chr2:178538651;178538650;178538649	chr2:179403378;179403377;179403376
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-129
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0936
• 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/K	None	None	0.317	N	0.765	0.549	0.818101870621	gnomAD-4.0.0	6.84226E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99502E-07	0	0
I/L	rs142108986	0.014	0.002	N	0.43	0.073	0.163833314356	gnomAD-2.1.1	1.78E-05	None	None	None	None	N	None	2.06748E-04	0	None	0	0	None	0	None	0	0	0
I/L	rs142108986	0.014	0.002	N	0.43	0.073	0.163833314356	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.93013E-04	0	0	0	0	None	0	0	0	0	0
I/L	rs142108986	0.014	0.002	N	0.43	0.073	0.163833314356	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/L	rs142108986	0.014	0.002	N	0.43	0.073	0.163833314356	gnomAD-4.0.0	1.17735E-05	None	None	None	None	N	None	2.39872E-04	0	None	0	0	None	0	0	0	0	1.60061E-05
I/R	rs763888823	None	0.484	D	0.791	0.583	0.834966523412	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
I/R	rs763888823	None	0.484	D	0.791	0.583	0.834966523412	gnomAD-4.0.0	6.57739E-06	None	None	None	None	N	None	2.41581E-05	0	None	0	0	None	0	0	0	0	0
I/T	rs763888823	None	0.062	N	0.709	0.37	0.609617904835	gnomAD-4.0.0	2.7369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69851E-06	1.15937E-05	0
I/V	None	None	None	N	0.184	0.062	0.230578612272	gnomAD-4.0.0	6.84219E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-07	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	0.2114	likely_benign	0.2706	benign	-1.797	Destabilizing	0.035	N	0.657	neutral	None	None	None	None	N
I/C	0.7171	likely_pathogenic	0.7585	pathogenic	-1.2	Destabilizing	0.824	D	0.735	prob.delet.	None	None	None	None	N
I/D	0.927	likely_pathogenic	0.962	pathogenic	-1.53	Destabilizing	0.555	D	0.789	deleterious	None	None	None	None	N
I/E	0.7981	likely_pathogenic	0.8862	pathogenic	-1.247	Destabilizing	0.555	D	0.781	deleterious	None	None	None	None	N
I/F	0.1922	likely_benign	0.2856	benign	-0.963	Destabilizing	0.38	N	0.71	prob.delet.	None	None	None	None	N
I/G	0.7858	likely_pathogenic	0.867	pathogenic	-2.367	Highly Destabilizing	0.555	D	0.765	deleterious	None	None	None	None	N
I/H	0.752	likely_pathogenic	0.8571	pathogenic	-1.946	Destabilizing	0.935	D	0.798	deleterious	None	None	None	None	N
I/K	0.6818	likely_pathogenic	0.822	pathogenic	-1.097	Destabilizing	0.317	N	0.765	deleterious	N	0.505316478	None	None	N
I/L	0.1131	likely_benign	0.1389	benign	-0.141	Destabilizing	0.002	N	0.43	neutral	N	0.466047039	None	None	N
I/M	0.0896	likely_benign	0.113	benign	-0.331	Destabilizing	0.002	N	0.304	neutral	N	0.475513522	None	None	N
I/N	0.6425	likely_pathogenic	0.7668	pathogenic	-1.569	Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/P	0.9189	likely_pathogenic	0.9458	pathogenic	-0.675	Destabilizing	0.791	D	0.789	deleterious	None	None	None	None	N
I/Q	0.6686	likely_pathogenic	0.7914	pathogenic	-1.233	Destabilizing	0.555	D	0.797	deleterious	None	None	None	None	N
I/R	0.587	likely_pathogenic	0.7431	pathogenic	-1.284	Destabilizing	0.484	N	0.791	deleterious	D	0.523420733	None	None	N
I/S	0.4291	ambiguous	0.5436	ambiguous	-2.323	Highly Destabilizing	0.149	N	0.746	deleterious	None	None	None	None	N
I/T	0.1614	likely_benign	0.2108	benign	-1.862	Destabilizing	0.062	N	0.709	prob.delet.	N	0.488933743	None	None	N
I/V	0.0605	likely_benign	0.0624	benign	-0.675	Destabilizing	None	N	0.184	neutral	N	0.40640409	None	None	N
I/W	0.8441	likely_pathogenic	0.9124	pathogenic	-1.25	Destabilizing	0.935	D	0.79	deleterious	None	None	None	None	N
I/Y	0.6767	likely_pathogenic	0.7942	pathogenic	-0.911	Destabilizing	0.555	D	0.755	deleterious	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.