TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33607	101044;101045;101046	chr2:178535796;178535795;178535794	chr2:179400523;179400522;179400521
N2AB	31966	96121;96122;96123	chr2:178535796;178535795;178535794	chr2:179400523;179400522;179400521
N2A	31039	93340;93341;93342	chr2:178535796;178535795;178535794	chr2:179400523;179400522;179400521
N2B	24542	73849;73850;73851	chr2:178535796;178535795;178535794	chr2:179400523;179400522;179400521
Novex-1	24667	74224;74225;74226	chr2:178535796;178535795;178535794	chr2:179400523;179400522;179400521
Novex-2	24734	74425;74426;74427	chr2:178535796;178535795;178535794	chr2:179400523;179400522;179400521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-159
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.115
• 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
A/V	None	None	1.0	N	0.62	0.351	0.5630262602	gnomAD-4.0.0	1.59605E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.91953E-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
A/C	0.6713	likely_pathogenic	0.515	ambiguous	-0.912	Destabilizing	0.979	D	0.406	neutral	None	None	None	None	N
A/D	0.9838	likely_pathogenic	0.957	pathogenic	-1.732	Destabilizing	1.0	D	0.717	prob.delet.	N	0.517603014	None	None	N
A/E	0.9733	likely_pathogenic	0.926	pathogenic	-1.727	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/F	0.9061	likely_pathogenic	0.8011	pathogenic	-1.052	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
A/G	0.3715	ambiguous	0.2916	benign	-1.358	Destabilizing	0.994	D	0.594	neutral	N	0.493965351	None	None	N
A/H	0.9627	likely_pathogenic	0.912	pathogenic	-1.67	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
A/I	0.7854	likely_pathogenic	0.6151	pathogenic	-0.366	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/K	0.9821	likely_pathogenic	0.9433	pathogenic	-1.454	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
A/L	0.7561	likely_pathogenic	0.5791	pathogenic	-0.366	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
A/M	0.8355	likely_pathogenic	0.6793	pathogenic	-0.233	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
A/N	0.9566	likely_pathogenic	0.8933	pathogenic	-1.209	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/P	0.9697	likely_pathogenic	0.9453	pathogenic	-0.555	Destabilizing	1.0	D	0.743	deleterious	N	0.517349525	None	None	N
A/Q	0.9435	likely_pathogenic	0.8627	pathogenic	-1.326	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/R	0.9511	likely_pathogenic	0.8756	pathogenic	-1.129	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
A/S	0.2945	likely_benign	0.2126	benign	-1.522	Destabilizing	0.992	D	0.601	neutral	N	0.493711861	None	None	N
A/T	0.4041	ambiguous	0.2518	benign	-1.429	Destabilizing	1.0	D	0.709	prob.delet.	N	0.485949954	None	None	N
A/V	0.4457	ambiguous	0.291	benign	-0.555	Destabilizing	1.0	D	0.62	neutral	N	0.466906336	None	None	N
A/W	0.9937	likely_pathogenic	0.9815	pathogenic	-1.52	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
A/Y	0.9636	likely_pathogenic	0.9144	pathogenic	-1.101	Destabilizing	1.0	D	0.731	prob.delet.	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.