TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29812	89659;89660;89661	chr2:178553571;178553570;178553569	chr2:179418298;179418297;179418296
N2AB	28171	84736;84737;84738	chr2:178553571;178553570;178553569	chr2:179418298;179418297;179418296
N2A	27244	81955;81956;81957	chr2:178553571;178553570;178553569	chr2:179418298;179418297;179418296
N2B	20747	62464;62465;62466	chr2:178553571;178553570;178553569	chr2:179418298;179418297;179418296
Novex-1	20872	62839;62840;62841	chr2:178553571;178553570;178553569	chr2:179418298;179418297;179418296
Novex-2	20939	63040;63041;63042	chr2:178553571;178553570;178553569	chr2:179418298;179418297;179418296
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: Fn3-105
• Domain position: 79
• Structural Position: 110
• Q(SASA): 0.0888
• 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/P	None	None	0.997	D	0.802	0.704	0.642082960585	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85814E-06	0	0
A/V	None	None	0.977	D	0.715	0.575	0.742137632746	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-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
A/C	0.8943	likely_pathogenic	0.903	pathogenic	-2.176	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/D	0.9968	likely_pathogenic	0.9975	pathogenic	-3.268	Highly Destabilizing	0.993	D	0.795	deleterious	D	0.555114971	None	None	N
A/E	0.996	likely_pathogenic	0.9967	pathogenic	-3.095	Highly Destabilizing	0.995	D	0.788	deleterious	None	None	None	None	N
A/F	0.9939	likely_pathogenic	0.9949	pathogenic	-0.897	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
A/G	0.4142	ambiguous	0.4178	ambiguous	-1.969	Destabilizing	0.955	D	0.627	neutral	N	0.517639013	None	None	N
A/H	0.9973	likely_pathogenic	0.9977	pathogenic	-1.769	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/I	0.9827	likely_pathogenic	0.9836	pathogenic	-0.591	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
A/K	0.999	likely_pathogenic	0.9992	pathogenic	-1.573	Destabilizing	0.995	D	0.786	deleterious	None	None	None	None	N
A/L	0.9468	likely_pathogenic	0.9569	pathogenic	-0.591	Destabilizing	0.983	D	0.764	deleterious	None	None	None	None	N
A/M	0.9742	likely_pathogenic	0.9757	pathogenic	-1.195	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
A/N	0.9917	likely_pathogenic	0.9927	pathogenic	-2.032	Highly Destabilizing	0.995	D	0.796	deleterious	None	None	None	None	N
A/P	0.9723	likely_pathogenic	0.9675	pathogenic	-0.892	Destabilizing	0.997	D	0.802	deleterious	D	0.528616925	None	None	N
A/Q	0.9918	likely_pathogenic	0.9935	pathogenic	-1.928	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
A/R	0.9948	likely_pathogenic	0.9958	pathogenic	-1.463	Destabilizing	0.995	D	0.808	deleterious	None	None	None	None	N
A/S	0.3165	likely_benign	0.3054	benign	-2.331	Highly Destabilizing	0.568	D	0.368	neutral	D	0.524093344	None	None	N
A/T	0.8311	likely_pathogenic	0.814	pathogenic	-2.058	Highly Destabilizing	0.955	D	0.651	neutral	D	0.532954884	None	None	N
A/V	0.8945	likely_pathogenic	0.896	pathogenic	-0.892	Destabilizing	0.977	D	0.715	prob.delet.	D	0.53472931	None	None	N
A/W	0.9992	likely_pathogenic	0.9995	pathogenic	-1.441	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/Y	0.9971	likely_pathogenic	0.9976	pathogenic	-1.088	Destabilizing	1.0	D	0.841	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.