TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26818	80677;80678;80679	chr2:178565680;178565679;178565678	chr2:179430407;179430406;179430405
N2AB	25177	75754;75755;75756	chr2:178565680;178565679;178565678	chr2:179430407;179430406;179430405
N2A	24250	72973;72974;72975	chr2:178565680;178565679;178565678	chr2:179430407;179430406;179430405
N2B	17753	53482;53483;53484	chr2:178565680;178565679;178565678	chr2:179430407;179430406;179430405
Novex-1	17878	53857;53858;53859	chr2:178565680;178565679;178565678	chr2:179430407;179430406;179430405
Novex-2	17945	54058;54059;54060	chr2:178565680;178565679;178565678	chr2:179430407;179430406;179430405
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-83
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0878
• 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
E/D	rs771164870	-1.881	0.998	N	0.676	0.41	0.373357554552	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs771164870	-1.881	0.998	N	0.676	0.41	0.373357554552	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
E/A	0.8317	likely_pathogenic	0.7392	pathogenic	-1.863	Destabilizing	1.0	D	0.761	deleterious	D	0.528772649	None	None	N
E/C	0.9785	likely_pathogenic	0.9715	pathogenic	-0.834	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/D	0.7228	likely_pathogenic	0.6547	pathogenic	-1.685	Destabilizing	0.998	D	0.676	prob.neutral	N	0.485575927	None	None	N
E/F	0.9891	likely_pathogenic	0.9832	pathogenic	-1.594	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
E/G	0.8932	likely_pathogenic	0.8345	pathogenic	-2.222	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.530547076	None	None	N
E/H	0.9614	likely_pathogenic	0.9512	pathogenic	-1.344	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/I	0.9725	likely_pathogenic	0.9531	pathogenic	-0.818	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/K	0.9289	likely_pathogenic	0.8993	pathogenic	-1.663	Destabilizing	1.0	D	0.695	prob.neutral	N	0.516148896	None	None	N
E/L	0.9531	likely_pathogenic	0.933	pathogenic	-0.818	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/M	0.9487	likely_pathogenic	0.9202	pathogenic	-0.049	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
E/N	0.9601	likely_pathogenic	0.9356	pathogenic	-1.788	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9989	pathogenic	-1.156	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/Q	0.6395	likely_pathogenic	0.5562	ambiguous	-1.517	Destabilizing	1.0	D	0.781	deleterious	N	0.47038128	None	None	N
E/R	0.9479	likely_pathogenic	0.9336	pathogenic	-1.469	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/S	0.8641	likely_pathogenic	0.7875	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/T	0.9497	likely_pathogenic	0.9132	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/V	0.9231	likely_pathogenic	0.8802	pathogenic	-1.156	Destabilizing	1.0	D	0.804	deleterious	N	0.521139327	None	None	N
E/W	0.9933	likely_pathogenic	0.9915	pathogenic	-1.655	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/Y	0.9787	likely_pathogenic	0.9714	pathogenic	-1.41	Destabilizing	1.0	D	0.858	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.