TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13987	42184;42185;42186	chr2:178635230;178635229;178635228	chr2:179499957;179499956;179499955
N2AB	12346	37261;37262;37263	chr2:178635230;178635229;178635228	chr2:179499957;179499956;179499955
N2A	11419	34480;34481;34482	chr2:178635230;178635229;178635228	chr2:179499957;179499956;179499955
N2B	4922	14989;14990;14991	chr2:178635230;178635229;178635228	chr2:179499957;179499956;179499955
Novex-1	5047	15364;15365;15366	chr2:178635230;178635229;178635228	chr2:179499957;179499956;179499955
Novex-2	5114	15565;15566;15567	chr2:178635230;178635229;178635228	chr2:179499957;179499956;179499955
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: Ig-90
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1948
• 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/A	rs2060288635	None	0.997	D	0.771	0.507	0.296679040009	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/A	rs2060288635	None	0.997	D	0.771	0.507	0.296679040009	gnomAD-4.0.0	6.57454E-06	None	None	None	None	N	None	2.41255E-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	0.5382	ambiguous	0.4441	ambiguous	-1.114	Destabilizing	0.997	D	0.771	deleterious	D	0.547683266	None	None	N
E/C	0.9753	likely_pathogenic	0.9685	pathogenic	-0.681	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/D	0.6762	likely_pathogenic	0.5628	ambiguous	-1.385	Destabilizing	0.997	D	0.667	prob.neutral	D	0.549232756	None	None	N
E/F	0.9597	likely_pathogenic	0.9461	pathogenic	-0.791	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
E/G	0.7919	likely_pathogenic	0.7218	pathogenic	-1.485	Destabilizing	0.999	D	0.803	deleterious	D	0.550207728	None	None	N
E/H	0.9265	likely_pathogenic	0.8863	pathogenic	-1.091	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/I	0.7103	likely_pathogenic	0.6293	pathogenic	-0.091	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
E/K	0.7096	likely_pathogenic	0.6142	pathogenic	-1.041	Destabilizing	0.997	D	0.69	prob.delet.	N	0.506786155	None	None	N
E/L	0.859	likely_pathogenic	0.7931	pathogenic	-0.091	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
E/M	0.8222	likely_pathogenic	0.7615	pathogenic	0.472	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/N	0.8459	likely_pathogenic	0.7431	pathogenic	-1.36	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
E/P	0.998	likely_pathogenic	0.9962	pathogenic	-0.412	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
E/Q	0.4254	ambiguous	0.3372	benign	-1.229	Destabilizing	0.999	D	0.69	prob.delet.	N	0.483130889	None	None	N
E/R	0.8286	likely_pathogenic	0.7733	pathogenic	-0.835	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
E/S	0.6512	likely_pathogenic	0.5303	ambiguous	-1.799	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
E/T	0.6405	likely_pathogenic	0.5135	ambiguous	-1.486	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
E/V	0.5005	ambiguous	0.4126	ambiguous	-0.412	Destabilizing	0.999	D	0.839	deleterious	N	0.466420263	None	None	N
E/W	0.991	likely_pathogenic	0.9879	pathogenic	-0.655	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/Y	0.9537	likely_pathogenic	0.9348	pathogenic	-0.562	Destabilizing	1.0	D	0.869	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.