TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18922	56989;56990;56991	chr2:178598946;178598945;178598944	chr2:179463673;179463672;179463671
N2AB	17281	52066;52067;52068	chr2:178598946;178598945;178598944	chr2:179463673;179463672;179463671
N2A	16354	49285;49286;49287	chr2:178598946;178598945;178598944	chr2:179463673;179463672;179463671
N2B	9857	29794;29795;29796	chr2:178598946;178598945;178598944	chr2:179463673;179463672;179463671
Novex-1	9982	30169;30170;30171	chr2:178598946;178598945;178598944	chr2:179463673;179463672;179463671
Novex-2	10049	30370;30371;30372	chr2:178598946;178598945;178598944	chr2:179463673;179463672;179463671
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: Fn3-25
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0927
• 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/D	rs776653576	None	0.999	N	0.656	0.272	0.443388199986	gnomAD-4.0.0	1.59327E-06	None	None	None	None	N	None	5.66187E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs761707154	-1.888	1.0	D	0.753	0.589	None	gnomAD-4.0.0	7.65409E-05	None	None	None	None	N	None	0	0	None	0	0	None	7.80239E-04	0	8.58212E-06	0	1.2133E-04

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	0.9619	likely_pathogenic	0.9584	pathogenic	-0.954	Destabilizing	0.999	D	0.699	prob.neutral	D	0.523835125	None	None	N
E/C	0.9951	likely_pathogenic	0.9952	pathogenic	-0.332	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.8966	likely_pathogenic	0.894	pathogenic	-1.824	Destabilizing	0.999	D	0.656	neutral	N	0.479486314	None	None	N
E/F	0.9976	likely_pathogenic	0.9975	pathogenic	-0.675	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/G	0.9801	likely_pathogenic	0.9753	pathogenic	-1.337	Destabilizing	1.0	D	0.753	deleterious	D	0.525609552	None	None	N
E/H	0.9907	likely_pathogenic	0.9887	pathogenic	-0.597	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/I	0.9942	likely_pathogenic	0.9925	pathogenic	0.138	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.9879	likely_pathogenic	0.983	pathogenic	-1.112	Destabilizing	0.999	D	0.676	prob.neutral	D	0.522567678	None	None	N
E/L	0.9916	likely_pathogenic	0.9898	pathogenic	0.138	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/M	0.9913	likely_pathogenic	0.991	pathogenic	0.736	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/N	0.9942	likely_pathogenic	0.9933	pathogenic	-1.439	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.212	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Q	0.8717	likely_pathogenic	0.838	pathogenic	-1.116	Destabilizing	1.0	D	0.762	deleterious	N	0.466266676	None	None	N
E/R	0.9867	likely_pathogenic	0.9817	pathogenic	-1.059	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/S	0.9778	likely_pathogenic	0.9764	pathogenic	-1.939	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/T	0.9907	likely_pathogenic	0.9889	pathogenic	-1.572	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/V	0.9826	likely_pathogenic	0.9771	pathogenic	-0.212	Destabilizing	1.0	D	0.751	deleterious	D	0.524595594	None	None	N
E/W	0.9987	likely_pathogenic	0.9986	pathogenic	-0.886	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.9961	likely_pathogenic	0.996	pathogenic	-0.516	Destabilizing	1.0	D	0.785	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.