TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31847	95764;95765;95766	chr2:178545571;178545570;178545569	chr2:179410298;179410297;179410296
N2AB	30206	90841;90842;90843	chr2:178545571;178545570;178545569	chr2:179410298;179410297;179410296
N2A	29279	88060;88061;88062	chr2:178545571;178545570;178545569	chr2:179410298;179410297;179410296
N2B	22782	68569;68570;68571	chr2:178545571;178545570;178545569	chr2:179410298;179410297;179410296
Novex-1	22907	68944;68945;68946	chr2:178545571;178545570;178545569	chr2:179410298;179410297;179410296
Novex-2	22974	69145;69146;69147	chr2:178545571;178545570;178545569	chr2:179410298;179410297;179410296
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-120
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0728
• 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
R/C	rs774814532	-1.7	1.0	N	0.919	0.535	0.437850553699	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	2.9E-05	None	0	2.22568E-04	None	0	None	0	8.87E-06	0
R/C	rs774814532	-1.7	1.0	N	0.919	0.535	0.437850553699	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92827E-04	None	0	0	0	0	0
R/C	rs774814532	-1.7	1.0	N	0.919	0.535	0.437850553699	gnomAD-4.0.0	1.36341E-05	None	None	None	None	N	None	0	1.66706E-05	None	0	1.78245E-04	None	0	3.29056E-04	9.3242E-06	0	0
R/H	rs771179752	-2.762	1.0	N	0.765	0.644	None	gnomAD-2.1.1	4.02E-05	None	None	None	None	N	None	0	0	None	0	1.11272E-04	None	3.27E-05	None	1.39237E-04	3.55E-05	0
R/H	rs771179752	-2.762	1.0	N	0.765	0.644	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
R/H	rs771179752	-2.762	1.0	N	0.765	0.644	None	gnomAD-4.0.0	4.46199E-05	None	None	None	None	N	None	0	1.66694E-05	None	0	3.11929E-04	None	7.80933E-05	6.58111E-04	3.8992E-05	2.19587E-05	0
R/P	rs771179752	None	1.0	D	0.873	0.749	0.565354849907	Rees (2021)	None	MmD	comp het with R5430*	None	None	N	Genetic analysis of TTN in 30 CM patients; comp het with truncating; Domain unfolded in vitro; cannot be re-folded	None	None	None	None	None	None	None	None	None	None	None
R/P	rs771179752	None	1.0	D	0.873	0.749	0.565354849907	gnomAD-4.0.0	6.84237E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99523E-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
R/A	0.9687	likely_pathogenic	0.9711	pathogenic	-2.169	Highly Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
R/C	0.5596	ambiguous	0.552	ambiguous	-1.946	Destabilizing	1.0	D	0.919	deleterious	N	0.489476721	None	None	N
R/D	0.9972	likely_pathogenic	0.9976	pathogenic	-0.81	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
R/E	0.9576	likely_pathogenic	0.964	pathogenic	-0.599	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	N
R/F	0.9611	likely_pathogenic	0.9624	pathogenic	-1.465	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
R/G	0.9595	likely_pathogenic	0.9613	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.715	prob.delet.	N	0.507985823	None	None	N
R/H	0.3992	ambiguous	0.4505	ambiguous	-2.204	Highly Destabilizing	1.0	D	0.765	deleterious	N	0.508492802	None	None	N
R/I	0.922	likely_pathogenic	0.9183	pathogenic	-1.166	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
R/K	0.2456	likely_benign	0.2398	benign	-1.291	Destabilizing	0.998	D	0.492	neutral	None	None	None	None	N
R/L	0.8152	likely_pathogenic	0.8153	pathogenic	-1.166	Destabilizing	1.0	D	0.715	prob.delet.	N	0.50903578	None	None	N
R/M	0.848	likely_pathogenic	0.846	pathogenic	-1.553	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
R/N	0.9861	likely_pathogenic	0.9894	pathogenic	-1.191	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
R/P	0.999	likely_pathogenic	0.9991	pathogenic	-1.49	Destabilizing	1.0	D	0.873	deleterious	D	0.532926933	None	None	N
R/Q	0.3785	ambiguous	0.386	ambiguous	-1.187	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
R/S	0.9901	likely_pathogenic	0.9908	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.707	prob.neutral	N	0.492600138	None	None	N
R/T	0.9704	likely_pathogenic	0.9714	pathogenic	-1.82	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
R/V	0.9371	likely_pathogenic	0.9343	pathogenic	-1.49	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
R/W	0.7096	likely_pathogenic	0.6883	pathogenic	-0.863	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
R/Y	0.8667	likely_pathogenic	0.8717	pathogenic	-0.758	Destabilizing	1.0	D	0.909	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.