TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15502	46729;46730;46731	chr2:178619813;178619812;178619811	chr2:179484540;179484539;179484538
N2AB	13861	41806;41807;41808	chr2:178619813;178619812;178619811	chr2:179484540;179484539;179484538
N2A	12934	39025;39026;39027	chr2:178619813;178619812;178619811	chr2:179484540;179484539;179484538
N2B	6437	19534;19535;19536	chr2:178619813;178619812;178619811	chr2:179484540;179484539;179484538
Novex-1	6562	19909;19910;19911	chr2:178619813;178619812;178619811	chr2:179484540;179484539;179484538
Novex-2	6629	20110;20111;20112	chr2:178619813;178619812;178619811	chr2:179484540;179484539;179484538
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-107
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2107
• 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	None	None	0.999	D	0.499	0.389	0.536988229258	gnomAD-4.0.0	6.84809E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16028E-05	0
E/Q	rs2057996369	None	1.0	D	0.597	0.342	0.423597194605	gnomAD-4.0.0	6.84809E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00087E-07	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	0.6634	likely_pathogenic	0.6952	pathogenic	-0.98	Destabilizing	0.999	D	0.625	neutral	D	0.572361583	None	None	N
E/C	0.9743	likely_pathogenic	0.9857	pathogenic	-0.67	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/D	0.8342	likely_pathogenic	0.8604	pathogenic	-1.452	Destabilizing	0.999	D	0.463	neutral	D	0.613618665	None	None	N
E/F	0.9724	likely_pathogenic	0.9846	pathogenic	-0.446	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/G	0.8746	likely_pathogenic	0.8701	pathogenic	-1.398	Destabilizing	1.0	D	0.727	prob.delet.	D	0.615900385	None	None	N
E/H	0.9331	likely_pathogenic	0.9465	pathogenic	-0.803	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.815	likely_pathogenic	0.8948	pathogenic	0.189	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/K	0.7984	likely_pathogenic	0.8332	pathogenic	-1.224	Destabilizing	0.999	D	0.499	neutral	D	0.567723416	None	None	N
E/L	0.9093	likely_pathogenic	0.9463	pathogenic	0.189	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/M	0.872	likely_pathogenic	0.9238	pathogenic	0.755	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/N	0.927	likely_pathogenic	0.948	pathogenic	-1.593	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/P	0.9969	likely_pathogenic	0.9958	pathogenic	-0.181	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Q	0.4686	ambiguous	0.5076	ambiguous	-1.371	Destabilizing	1.0	D	0.597	neutral	D	0.544488135	None	None	N
E/R	0.8647	likely_pathogenic	0.8865	pathogenic	-0.992	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/S	0.7502	likely_pathogenic	0.7699	pathogenic	-2.067	Highly Destabilizing	0.999	D	0.555	neutral	None	None	None	None	N
E/T	0.7693	likely_pathogenic	0.8262	pathogenic	-1.712	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/V	0.6214	likely_pathogenic	0.7411	pathogenic	-0.181	Destabilizing	1.0	D	0.76	deleterious	D	0.533657306	None	None	N
E/W	0.9925	likely_pathogenic	0.9957	pathogenic	-0.356	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.9602	likely_pathogenic	0.9729	pathogenic	-0.242	Destabilizing	1.0	D	0.773	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.