TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17900	53923;53924;53925	chr2:178605597;178605596;178605595	chr2:179470324;179470323;179470322
N2AB	16259	49000;49001;49002	chr2:178605597;178605596;178605595	chr2:179470324;179470323;179470322
N2A	15332	46219;46220;46221	chr2:178605597;178605596;178605595	chr2:179470324;179470323;179470322
N2B	8835	26728;26729;26730	chr2:178605597;178605596;178605595	chr2:179470324;179470323;179470322
Novex-1	8960	27103;27104;27105	chr2:178605597;178605596;178605595	chr2:179470324;179470323;179470322
Novex-2	9027	27304;27305;27306	chr2:178605597;178605596;178605595	chr2:179470324;179470323;179470322
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: Fn3-18
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.145
• 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/Q	rs1231539821	None	0.997	N	0.777	0.218	0.276898752692	gnomAD-3.1.2	6.63E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.48E-05	0	0
E/Q	rs1231539821	None	0.997	N	0.777	0.218	0.276898752692	gnomAD-4.0.0	6.6306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47658E-05	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	0.9367	likely_pathogenic	0.9158	pathogenic	-1.313	Destabilizing	0.977	D	0.687	prob.neutral	N	0.51807468	None	None	N
E/C	0.987	likely_pathogenic	0.986	pathogenic	-0.697	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/D	0.7241	likely_pathogenic	0.6505	pathogenic	-1.842	Destabilizing	0.117	N	0.379	neutral	N	0.471586275	None	None	N
E/F	0.9914	likely_pathogenic	0.9906	pathogenic	-0.905	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/G	0.9579	likely_pathogenic	0.9417	pathogenic	-1.721	Destabilizing	0.993	D	0.734	prob.delet.	N	0.513101158	None	None	N
E/H	0.9769	likely_pathogenic	0.9677	pathogenic	-0.898	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/I	0.9727	likely_pathogenic	0.9683	pathogenic	-0.143	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
E/K	0.9578	likely_pathogenic	0.9382	pathogenic	-1.5	Destabilizing	0.977	D	0.677	prob.neutral	N	0.47730704	None	None	N
E/L	0.9712	likely_pathogenic	0.9658	pathogenic	-0.143	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
E/M	0.9717	likely_pathogenic	0.9657	pathogenic	0.554	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/N	0.9727	likely_pathogenic	0.9618	pathogenic	-1.802	Destabilizing	0.99	D	0.794	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9996	pathogenic	-0.518	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
E/Q	0.7256	likely_pathogenic	0.6608	pathogenic	-1.5	Destabilizing	0.997	D	0.777	deleterious	N	0.51222762	None	None	N
E/R	0.965	likely_pathogenic	0.9518	pathogenic	-1.315	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
E/S	0.9311	likely_pathogenic	0.8986	pathogenic	-2.385	Highly Destabilizing	0.983	D	0.68	prob.neutral	None	None	None	None	N
E/T	0.9563	likely_pathogenic	0.9394	pathogenic	-2.005	Highly Destabilizing	0.995	D	0.78	deleterious	None	None	None	None	N
E/V	0.9345	likely_pathogenic	0.9215	pathogenic	-0.518	Destabilizing	0.997	D	0.78	deleterious	N	0.498097548	None	None	N
E/W	0.9935	likely_pathogenic	0.9916	pathogenic	-0.994	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/Y	0.984	likely_pathogenic	0.9801	pathogenic	-0.726	Destabilizing	1.0	D	0.801	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.