TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16435	49528;49529;49530	chr2:178614094;178614093;178614092	chr2:179478821;179478820;179478819
N2AB	14794	44605;44606;44607	chr2:178614094;178614093;178614092	chr2:179478821;179478820;179478819
N2A	13867	41824;41825;41826	chr2:178614094;178614093;178614092	chr2:179478821;179478820;179478819
N2B	7370	22333;22334;22335	chr2:178614094;178614093;178614092	chr2:179478821;179478820;179478819
Novex-1	7495	22708;22709;22710	chr2:178614094;178614093;178614092	chr2:179478821;179478820;179478819
Novex-2	7562	22909;22910;22911	chr2:178614094;178614093;178614092	chr2:179478821;179478820;179478819
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: Fn3-6
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.5828
• 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	rs1407270484	None	0.906	N	0.407	0.142	0.283371740733	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/D	rs1407270484	None	0.906	N	0.407	0.142	0.283371740733	gnomAD-4.0.0	2.03037E-06	None	None	None	None	N	None	0	6.16599E-05	None	0	0	None	0	0	1.20507E-06	0	0
E/K	rs886044255	None	0.92	N	0.432	0.288	0.276482976112	gnomAD-4.0.0	3.42356E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49919E-06	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	0.2095	likely_benign	0.1745	benign	-0.366	Destabilizing	0.061	N	0.192	neutral	N	0.46839016	None	None	N
E/C	0.8624	likely_pathogenic	0.8189	pathogenic	-0.123	Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
E/D	0.0899	likely_benign	0.0833	benign	-0.36	Destabilizing	0.906	D	0.407	neutral	N	0.484201495	None	None	N
E/F	0.7807	likely_pathogenic	0.7237	pathogenic	-0.219	Destabilizing	0.997	D	0.491	neutral	None	None	None	None	N
E/G	0.3391	likely_benign	0.2654	benign	-0.565	Destabilizing	0.852	D	0.453	neutral	D	0.596234689	None	None	N
E/H	0.6335	likely_pathogenic	0.5551	ambiguous	0.058	Stabilizing	0.997	D	0.466	neutral	None	None	None	None	N
E/I	0.3215	likely_benign	0.2748	benign	0.123	Stabilizing	0.982	D	0.512	neutral	None	None	None	None	N
E/K	0.2479	likely_benign	0.1964	benign	0.245	Stabilizing	0.92	D	0.432	neutral	N	0.500683274	None	None	N
E/L	0.3984	ambiguous	0.3425	ambiguous	0.123	Stabilizing	0.939	D	0.511	neutral	None	None	None	None	N
E/M	0.4758	ambiguous	0.4241	ambiguous	0.157	Stabilizing	0.999	D	0.493	neutral	None	None	None	None	N
E/N	0.2648	likely_benign	0.2212	benign	-0.056	Destabilizing	0.969	D	0.501	neutral	None	None	None	None	N
E/P	0.3747	ambiguous	0.3342	benign	-0.02	Destabilizing	0.046	N	0.213	neutral	None	None	None	None	N
E/Q	0.215	likely_benign	0.1809	benign	-0.023	Destabilizing	0.986	D	0.533	neutral	N	0.472965374	None	None	N
E/R	0.4689	ambiguous	0.3862	ambiguous	0.498	Stabilizing	0.991	D	0.489	neutral	None	None	None	None	N
E/S	0.2511	likely_benign	0.2089	benign	-0.231	Destabilizing	0.759	D	0.427	neutral	None	None	None	None	N
E/T	0.2783	likely_benign	0.2374	benign	-0.07	Destabilizing	0.17	N	0.217	neutral	None	None	None	None	N
E/V	0.2141	likely_benign	0.1824	benign	-0.02	Destabilizing	0.92	D	0.477	neutral	N	0.472414888	None	None	N
E/W	0.9439	likely_pathogenic	0.9227	pathogenic	-0.066	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
E/Y	0.6751	likely_pathogenic	0.6006	pathogenic	0.023	Stabilizing	0.997	D	0.486	neutral	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.