TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30460	91603;91604;91605	chr2:178551153;178551152;178551151	chr2:179415880;179415879;179415878
N2AB	28819	86680;86681;86682	chr2:178551153;178551152;178551151	chr2:179415880;179415879;179415878
N2A	27892	83899;83900;83901	chr2:178551153;178551152;178551151	chr2:179415880;179415879;179415878
N2B	21395	64408;64409;64410	chr2:178551153;178551152;178551151	chr2:179415880;179415879;179415878
Novex-1	21520	64783;64784;64785	chr2:178551153;178551152;178551151	chr2:179415880;179415879;179415878
Novex-2	21587	64984;64985;64986	chr2:178551153;178551152;178551151	chr2:179415880;179415879;179415878
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-110
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1873
• 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/K	rs908278682	-1.21	0.999	D	0.669	0.461	0.378322506985	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs908278682	-1.21	0.999	D	0.669	0.461	0.378322506985	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs908278682	-1.21	0.999	D	0.669	0.461	0.378322506985	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	2.41394E-05	0	None	0	0	None	0	0	0	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
E/A	0.9586	likely_pathogenic	0.964	pathogenic	-1.781	Destabilizing	0.999	D	0.685	prob.neutral	D	0.545560231	None	None	N
E/C	0.9923	likely_pathogenic	0.9924	pathogenic	-0.93	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/D	0.9267	likely_pathogenic	0.9248	pathogenic	-1.845	Destabilizing	0.999	D	0.632	neutral	N	0.483930085	None	None	N
E/F	0.9955	likely_pathogenic	0.995	pathogenic	-1.461	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/G	0.9679	likely_pathogenic	0.9731	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.759	deleterious	D	0.535813768	None	None	N
E/H	0.9886	likely_pathogenic	0.9882	pathogenic	-1.311	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/I	0.984	likely_pathogenic	0.984	pathogenic	-0.679	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/K	0.9723	likely_pathogenic	0.9769	pathogenic	-1.761	Destabilizing	0.999	D	0.669	neutral	D	0.526188529	None	None	N
E/L	0.9813	likely_pathogenic	0.9806	pathogenic	-0.679	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/M	0.9821	likely_pathogenic	0.9822	pathogenic	0.091	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/N	0.9918	likely_pathogenic	0.9915	pathogenic	-1.957	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9998	pathogenic	-1.034	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/Q	0.7828	likely_pathogenic	0.7816	pathogenic	-1.676	Destabilizing	1.0	D	0.745	deleterious	N	0.467583349	None	None	N
E/R	0.9711	likely_pathogenic	0.9751	pathogenic	-1.538	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/S	0.9635	likely_pathogenic	0.965	pathogenic	-2.596	Highly Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
E/T	0.9818	likely_pathogenic	0.9823	pathogenic	-2.232	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/V	0.9659	likely_pathogenic	0.967	pathogenic	-1.034	Destabilizing	1.0	D	0.757	deleterious	D	0.528216445	None	None	N
E/W	0.9975	likely_pathogenic	0.9975	pathogenic	-1.518	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.9934	likely_pathogenic	0.9929	pathogenic	-1.282	Destabilizing	1.0	D	0.791	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.