TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26671	80236;80237;80238	chr2:178566121;178566120;178566119	chr2:179430848;179430847;179430846
N2AB	25030	75313;75314;75315	chr2:178566121;178566120;178566119	chr2:179430848;179430847;179430846
N2A	24103	72532;72533;72534	chr2:178566121;178566120;178566119	chr2:179430848;179430847;179430846
N2B	17606	53041;53042;53043	chr2:178566121;178566120;178566119	chr2:179430848;179430847;179430846
Novex-1	17731	53416;53417;53418	chr2:178566121;178566120;178566119	chr2:179430848;179430847;179430846
Novex-2	17798	53617;53618;53619	chr2:178566121;178566120;178566119	chr2:179430848;179430847;179430846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-138
• Domain position: 78
• Structural Position: 165
• Q(SASA): 0.4394
• 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/P	rs371983237	-0.375	0.667	N	0.46	0.378	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-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
S/A	0.0834	likely_benign	0.0848	benign	-0.34	Destabilizing	0.055	N	0.314	neutral	N	0.517820733	None	None	N
S/C	0.0774	likely_benign	0.083	benign	-0.232	Destabilizing	0.909	D	0.507	neutral	None	None	None	None	N
S/D	0.4461	ambiguous	0.3971	ambiguous	0.046	Stabilizing	0.272	N	0.356	neutral	None	None	None	None	N
S/E	0.4173	ambiguous	0.3717	ambiguous	-0.057	Destabilizing	0.272	N	0.353	neutral	None	None	None	None	N
S/F	0.1588	likely_benign	0.1503	benign	-0.967	Destabilizing	0.726	D	0.627	neutral	None	None	None	None	N
S/G	0.1071	likely_benign	0.1109	benign	-0.436	Destabilizing	0.272	N	0.333	neutral	None	None	None	None	N
S/H	0.3029	likely_benign	0.2749	benign	-0.968	Destabilizing	0.968	D	0.503	neutral	None	None	None	None	N
S/I	0.113	likely_benign	0.1113	benign	-0.216	Destabilizing	0.396	N	0.568	neutral	None	None	None	None	N
S/K	0.5147	ambiguous	0.4738	ambiguous	-0.467	Destabilizing	0.272	N	0.353	neutral	None	None	None	None	N
S/L	0.0947	likely_benign	0.0926	benign	-0.216	Destabilizing	0.124	N	0.557	neutral	N	0.501407636	None	None	N
S/M	0.1391	likely_benign	0.1382	benign	0.078	Stabilizing	0.909	D	0.51	neutral	None	None	None	None	N
S/N	0.1216	likely_benign	0.1115	benign	-0.156	Destabilizing	0.272	N	0.386	neutral	None	None	None	None	N
S/P	0.7271	likely_pathogenic	0.6652	pathogenic	-0.23	Destabilizing	0.667	D	0.46	neutral	N	0.51976538	None	None	N
S/Q	0.3544	ambiguous	0.3242	benign	-0.442	Destabilizing	0.726	D	0.427	neutral	None	None	None	None	N
S/R	0.483	ambiguous	0.434	ambiguous	-0.242	Destabilizing	0.567	D	0.468	neutral	None	None	None	None	N
S/T	0.0693	likely_benign	0.0668	benign	-0.269	Destabilizing	None	N	0.17	neutral	N	0.453617326	None	None	N
S/V	0.1228	likely_benign	0.1215	benign	-0.23	Destabilizing	0.157	N	0.545	neutral	None	None	None	None	N
S/W	0.3547	ambiguous	0.3453	ambiguous	-0.976	Destabilizing	0.968	D	0.675	prob.neutral	None	None	None	None	N
S/Y	0.184	likely_benign	0.1749	benign	-0.695	Destabilizing	0.726	D	0.633	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.