TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35496	106711;106712;106713	chr2:178530005;178530004;178530003	chr2:179394732;179394731;179394730
N2AB	33855	101788;101789;101790	chr2:178530005;178530004;178530003	chr2:179394732;179394731;179394730
N2A	32928	99007;99008;99009	chr2:178530005;178530004;178530003	chr2:179394732;179394731;179394730
N2B	26431	79516;79517;79518	chr2:178530005;178530004;178530003	chr2:179394732;179394731;179394730
Novex-1	26556	79891;79892;79893	chr2:178530005;178530004;178530003	chr2:179394732;179394731;179394730
Novex-2	26623	80092;80093;80094	chr2:178530005;178530004;178530003	chr2:179394732;179394731;179394730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-166
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.0801
• 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
N/K	None	None	0.997	D	0.67	0.413	0.191931220699	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.9788	likely_pathogenic	0.976	pathogenic	-0.619	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
N/C	0.9613	likely_pathogenic	0.96	pathogenic	-0.144	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/D	0.8709	likely_pathogenic	0.8587	pathogenic	-1.536	Destabilizing	0.997	D	0.561	neutral	D	0.531192186	None	None	N
N/E	0.9907	likely_pathogenic	0.99	pathogenic	-1.466	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
N/F	0.9959	likely_pathogenic	0.996	pathogenic	-0.7	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
N/G	0.9433	likely_pathogenic	0.9411	pathogenic	-0.897	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	N
N/H	0.9342	likely_pathogenic	0.926	pathogenic	-0.796	Destabilizing	0.999	D	0.779	deleterious	D	0.543980523	None	None	N
N/I	0.9623	likely_pathogenic	0.9609	pathogenic	0.065	Stabilizing	0.999	D	0.801	deleterious	D	0.544234013	None	None	N
N/K	0.9913	likely_pathogenic	0.9913	pathogenic	-0.228	Destabilizing	0.997	D	0.67	neutral	D	0.543473544	None	None	N
N/L	0.9595	likely_pathogenic	0.9617	pathogenic	0.065	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
N/M	0.9775	likely_pathogenic	0.9778	pathogenic	0.625	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
N/P	0.9952	likely_pathogenic	0.9946	pathogenic	-0.135	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
N/Q	0.9925	likely_pathogenic	0.9922	pathogenic	-1.151	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
N/R	0.9929	likely_pathogenic	0.9928	pathogenic	-0.079	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
N/S	0.6783	likely_pathogenic	0.6445	pathogenic	-0.831	Destabilizing	0.997	D	0.567	neutral	N	0.478663393	None	None	N
N/T	0.8454	likely_pathogenic	0.8279	pathogenic	-0.609	Destabilizing	0.997	D	0.659	neutral	N	0.501985115	None	None	N
N/V	0.9652	likely_pathogenic	0.9632	pathogenic	-0.135	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
N/W	0.9988	likely_pathogenic	0.9988	pathogenic	-0.564	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/Y	0.9456	likely_pathogenic	0.9439	pathogenic	-0.245	Destabilizing	0.999	D	0.815	deleterious	D	0.543980523	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.