TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5890	17893;17894;17895	chr2:178730997;178730996;178730995	chr2:179595724;179595723;179595722
N2AB	5573	16942;16943;16944	chr2:178730997;178730996;178730995	chr2:179595724;179595723;179595722
N2A	4646	14161;14162;14163	chr2:178730997;178730996;178730995	chr2:179595724;179595723;179595722
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-42
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3538
• 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
S/T	rs775293848	-0.426	0.961	N	0.473	0.235	0.262662153117	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	2.61081E-04	None	0	0	None	0	None	0	0	0
S/T	rs775293848	-0.426	0.961	N	0.473	0.235	0.262662153117	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
S/T	rs775293848	-0.426	0.961	N	0.473	0.235	0.262662153117	gnomAD-4.0.0	1.28158E-05	None	None	None	None	N	None	0	1.69509E-04	None	0	0	None	0	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
S/A	0.0714	likely_benign	0.0822	benign	-0.759	Destabilizing	0.304	N	0.145	neutral	None	None	None	None	N
S/C	0.1243	likely_benign	0.1622	benign	-0.511	Destabilizing	1.0	D	0.569	neutral	N	0.500473038	None	None	N
S/D	0.4925	ambiguous	0.5857	pathogenic	-0.314	Destabilizing	0.985	D	0.437	neutral	None	None	None	None	N
S/E	0.5705	likely_pathogenic	0.6396	pathogenic	-0.315	Destabilizing	0.97	D	0.448	neutral	None	None	None	None	N
S/F	0.3319	likely_benign	0.4409	ambiguous	-0.945	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
S/G	0.0873	likely_benign	0.0991	benign	-1.01	Destabilizing	0.071	N	0.141	neutral	N	0.485345742	None	None	N
S/H	0.5107	ambiguous	0.5585	ambiguous	-1.468	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
S/I	0.2302	likely_benign	0.2948	benign	-0.197	Destabilizing	0.994	D	0.633	neutral	N	0.493218109	None	None	N
S/K	0.6971	likely_pathogenic	0.7667	pathogenic	-0.712	Destabilizing	0.942	D	0.445	neutral	None	None	None	None	N
S/L	0.1367	likely_benign	0.1792	benign	-0.197	Destabilizing	0.97	D	0.557	neutral	None	None	None	None	N
S/M	0.2315	likely_benign	0.2641	benign	0.128	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	N
S/N	0.1854	likely_benign	0.222	benign	-0.692	Destabilizing	0.98	D	0.467	neutral	N	0.485620785	None	None	N
S/P	0.8531	likely_pathogenic	0.9083	pathogenic	-0.35	Destabilizing	0.996	D	0.575	neutral	None	None	None	None	N
S/Q	0.5768	likely_pathogenic	0.6057	pathogenic	-0.854	Destabilizing	0.991	D	0.478	neutral	None	None	None	None	N
S/R	0.5498	ambiguous	0.6156	pathogenic	-0.586	Destabilizing	0.151	N	0.268	neutral	N	0.50372504	None	None	N
S/T	0.0926	likely_benign	0.1046	benign	-0.716	Destabilizing	0.961	D	0.473	neutral	N	0.499371045	None	None	N
S/V	0.2584	likely_benign	0.3196	benign	-0.35	Destabilizing	0.97	D	0.572	neutral	None	None	None	None	N
S/W	0.5505	ambiguous	0.6049	pathogenic	-0.911	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
S/Y	0.3239	likely_benign	0.4226	ambiguous	-0.65	Destabilizing	0.999	D	0.645	neutral	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.