TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6871	20836;20837;20838	chr2:178725593;178725592;178725591	chr2:179590320;179590319;179590318
N2AB	6554	19885;19886;19887	chr2:178725593;178725592;178725591	chr2:179590320;179590319;179590318
N2A	5627	17104;17105;17106	chr2:178725593;178725592;178725591	chr2:179590320;179590319;179590318
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-53
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.3238
• 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/T	rs745807060	-1.034	0.183	N	0.537	0.131	0.119812018005	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	6.49E-05	0	None	0	0	None	0	None	0	0	0
A/T	rs745807060	-1.034	0.183	N	0.537	0.131	0.119812018005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs745807060	-1.034	0.183	N	0.537	0.131	0.119812018005	gnomAD-4.0.0	2.57169E-06	None	None	None	None	N	None	3.39029E-05	0	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
A/C	0.4683	ambiguous	0.4787	ambiguous	-0.964	Destabilizing	0.836	D	0.644	neutral	None	None	None	None	N
A/D	0.8778	likely_pathogenic	0.8718	pathogenic	-1.154	Destabilizing	0.921	D	0.703	prob.neutral	N	0.478764028	None	None	N
A/E	0.75	likely_pathogenic	0.7424	pathogenic	-1.075	Destabilizing	0.593	D	0.673	neutral	None	None	None	None	N
A/F	0.4698	ambiguous	0.4789	ambiguous	-0.69	Destabilizing	0.716	D	0.699	prob.neutral	None	None	None	None	N
A/G	0.2628	likely_benign	0.2484	benign	-1.265	Destabilizing	0.523	D	0.547	neutral	N	0.478257048	None	None	N
A/H	0.8669	likely_pathogenic	0.8595	pathogenic	-1.439	Destabilizing	0.983	D	0.683	prob.neutral	None	None	None	None	N
A/I	0.189	likely_benign	0.1786	benign	0.053	Stabilizing	0.049	N	0.454	neutral	None	None	None	None	N
A/K	0.8512	likely_pathogenic	0.851	pathogenic	-1.157	Destabilizing	0.593	D	0.643	neutral	None	None	None	None	N
A/L	0.2021	likely_benign	0.2088	benign	0.053	Stabilizing	None	N	0.33	neutral	None	None	None	None	N
A/M	0.2594	likely_benign	0.2422	benign	-0.099	Destabilizing	0.061	N	0.391	neutral	None	None	None	None	N
A/N	0.7836	likely_pathogenic	0.7576	pathogenic	-1.072	Destabilizing	0.94	D	0.701	prob.neutral	None	None	None	None	N
A/P	0.8497	likely_pathogenic	0.8719	pathogenic	-0.213	Destabilizing	0.921	D	0.723	prob.delet.	N	0.478510538	None	None	N
A/Q	0.7455	likely_pathogenic	0.7381	pathogenic	-1.046	Destabilizing	0.836	D	0.715	prob.delet.	None	None	None	None	N
A/R	0.7804	likely_pathogenic	0.7904	pathogenic	-1.02	Destabilizing	0.836	D	0.723	prob.delet.	None	None	None	None	N
A/S	0.2037	likely_benign	0.1897	benign	-1.547	Destabilizing	0.351	N	0.563	neutral	N	0.478257048	None	None	N
A/T	0.1128	likely_benign	0.107	benign	-1.337	Destabilizing	0.183	N	0.537	neutral	N	0.48403258	None	None	N
A/V	0.0821	likely_benign	0.0822	benign	-0.213	Destabilizing	0.001	N	0.155	neutral	N	0.371915009	None	None	N
A/W	0.8994	likely_pathogenic	0.9042	pathogenic	-1.183	Destabilizing	0.983	D	0.709	prob.delet.	None	None	None	None	N
A/Y	0.7747	likely_pathogenic	0.765	pathogenic	-0.688	Destabilizing	0.836	D	0.697	prob.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.