TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8623	26092;26093;26094	chr2:178715547;178715546;178715545	chr2:179580274;179580273;179580272
N2AB	8306	25141;25142;25143	chr2:178715547;178715546;178715545	chr2:179580274;179580273;179580272
N2A	7379	22360;22361;22362	chr2:178715547;178715546;178715545	chr2:179580274;179580273;179580272
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-71
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.2547
• 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	None	None	0.969	N	0.508	0.325	0.36453787251	gnomAD-4.0.0	1.36861E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79919E-06	0	0
E/G	rs766190373	-1.849	0.998	D	0.681	0.478	0.65995756008	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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
E/A	0.417	ambiguous	0.3833	ambiguous	-0.969	Destabilizing	0.619	D	0.389	neutral	N	0.52101592	None	None	N
E/C	0.9695	likely_pathogenic	0.9533	pathogenic	-0.602	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/D	0.5638	ambiguous	0.5355	ambiguous	-1.458	Destabilizing	0.969	D	0.508	neutral	N	0.521776389	None	None	N
E/F	0.901	likely_pathogenic	0.8703	pathogenic	-0.466	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/G	0.6709	likely_pathogenic	0.6183	pathogenic	-1.405	Destabilizing	0.998	D	0.681	prob.neutral	D	0.540387623	None	None	N
E/H	0.7113	likely_pathogenic	0.6675	pathogenic	-0.833	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/I	0.471	ambiguous	0.4248	ambiguous	0.25	Stabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
E/K	0.22	likely_benign	0.2111	benign	-1.065	Destabilizing	0.998	D	0.572	neutral	N	0.489977984	None	None	N
E/L	0.631	likely_pathogenic	0.5904	pathogenic	0.25	Stabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
E/M	0.5996	likely_pathogenic	0.5791	pathogenic	0.894	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/N	0.7154	likely_pathogenic	0.6854	pathogenic	-1.514	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.9974	likely_pathogenic	0.9968	pathogenic	-0.136	Destabilizing	0.993	D	0.812	deleterious	None	None	None	None	N
E/Q	0.2111	likely_benign	0.1953	benign	-1.269	Destabilizing	1.0	D	0.671	neutral	N	0.517260585	None	None	N
E/R	0.4135	ambiguous	0.3803	ambiguous	-0.891	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/S	0.5589	ambiguous	0.524	ambiguous	-2.009	Highly Destabilizing	0.988	D	0.567	neutral	None	None	None	None	N
E/T	0.4814	ambiguous	0.4439	ambiguous	-1.626	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/V	0.2931	likely_benign	0.2642	benign	-0.136	Destabilizing	0.996	D	0.759	deleterious	N	0.478723627	None	None	N
E/W	0.9756	likely_pathogenic	0.9649	pathogenic	-0.366	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Y	0.8699	likely_pathogenic	0.8339	pathogenic	-0.241	Destabilizing	1.0	D	0.829	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.