TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20721	62386;62387;62388	chr2:178589564;178589563;178589562	chr2:179454291;179454290;179454289
N2AB	19080	57463;57464;57465	chr2:178589564;178589563;178589562	chr2:179454291;179454290;179454289
N2A	18153	54682;54683;54684	chr2:178589564;178589563;178589562	chr2:179454291;179454290;179454289
N2B	11656	35191;35192;35193	chr2:178589564;178589563;178589562	chr2:179454291;179454290;179454289
Novex-1	11781	35566;35567;35568	chr2:178589564;178589563;178589562	chr2:179454291;179454290;179454289
Novex-2	11848	35767;35768;35769	chr2:178589564;178589563;178589562	chr2:179454291;179454290;179454289
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-38
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.401
• 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
G/A	rs1656930545	None	0.992	N	0.487	0.318	0.293502639404	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
G/A	rs1656930545	None	0.992	N	0.487	0.318	0.293502639404	gnomAD-4.0.0	6.58051E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.41974E-05	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
G/A	0.242	likely_benign	0.4123	ambiguous	-0.267	Destabilizing	0.992	D	0.487	neutral	N	0.499391609	None	None	N
G/C	0.5234	ambiguous	0.7505	pathogenic	-0.678	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/D	0.4976	ambiguous	0.6397	pathogenic	-0.913	Destabilizing	0.702	D	0.353	neutral	None	None	None	None	N
G/E	0.5872	likely_pathogenic	0.7436	pathogenic	-1.063	Destabilizing	0.998	D	0.636	neutral	N	0.478709692	None	None	N
G/F	0.8279	likely_pathogenic	0.9226	pathogenic	-1.009	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/H	0.748	likely_pathogenic	0.8883	pathogenic	-0.602	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
G/I	0.598	likely_pathogenic	0.7764	pathogenic	-0.371	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
G/K	0.844	likely_pathogenic	0.9186	pathogenic	-0.909	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
G/L	0.7394	likely_pathogenic	0.8695	pathogenic	-0.371	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/M	0.7248	likely_pathogenic	0.8709	pathogenic	-0.473	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
G/N	0.4411	ambiguous	0.6438	pathogenic	-0.443	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
G/P	0.9526	likely_pathogenic	0.9668	pathogenic	-0.304	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
G/Q	0.7114	likely_pathogenic	0.85	pathogenic	-0.733	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/R	0.8147	likely_pathogenic	0.9084	pathogenic	-0.45	Destabilizing	0.999	D	0.721	prob.delet.	N	0.490292123	None	None	N
G/S	0.1829	likely_benign	0.3676	ambiguous	-0.504	Destabilizing	0.967	D	0.363	neutral	None	None	None	None	N
G/T	0.3158	likely_benign	0.5134	ambiguous	-0.596	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
G/V	0.4575	ambiguous	0.6525	pathogenic	-0.304	Destabilizing	0.999	D	0.722	prob.delet.	N	0.452923026	None	None	N
G/W	0.7831	likely_pathogenic	0.8939	pathogenic	-1.206	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
G/Y	0.6976	likely_pathogenic	0.8617	pathogenic	-0.847	Destabilizing	1.0	D	0.769	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.