TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8673	26242;26243;26244	chr2:178715169;178715168;178715167	chr2:179579896;179579895;179579894
N2AB	8356	25291;25292;25293	chr2:178715169;178715168;178715167	chr2:179579896;179579895;179579894
N2A	7429	22510;22511;22512	chr2:178715169;178715168;178715167	chr2:179579896;179579895;179579894
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-72
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.8926
• Predicted PPI site: I

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
H/Q	rs370266918	0.375	None	N	0.055	0.107	0.0482279557977	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65618E-04
H/Q	rs370266918	0.375	None	N	0.055	0.107	0.0482279557977	gnomAD-4.0.0	1.36848E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73491E-04	8.99522E-07	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
H/A	0.1156	likely_benign	0.1173	benign	0.435	Stabilizing	0.002	N	0.273	neutral	None	None	None	None	I
H/C	0.1368	likely_benign	0.1421	benign	0.746	Stabilizing	0.497	N	0.399	neutral	None	None	None	None	I
H/D	0.1068	likely_benign	0.1166	benign	-0.027	Destabilizing	0.001	N	0.251	neutral	N	0.416808377	None	None	I
H/E	0.1121	likely_benign	0.1163	benign	-0.009	Destabilizing	None	N	0.046	neutral	None	None	None	None	I
H/F	0.2118	likely_benign	0.2021	benign	1.056	Stabilizing	0.044	N	0.429	neutral	None	None	None	None	I
H/G	0.1782	likely_benign	0.1775	benign	0.172	Stabilizing	0.008	N	0.27	neutral	None	None	None	None	I
H/I	0.1282	likely_benign	0.1319	benign	1.097	Stabilizing	0.009	N	0.298	neutral	None	None	None	None	I
H/K	0.1168	likely_benign	0.116	benign	0.351	Stabilizing	0.002	N	0.275	neutral	None	None	None	None	I
H/L	0.0646	likely_benign	0.0699	benign	1.097	Stabilizing	None	N	0.261	neutral	N	0.434087415	None	None	I
H/M	0.2223	likely_benign	0.2291	benign	0.788	Stabilizing	0.044	N	0.522	neutral	None	None	None	None	I
H/N	0.0632	likely_benign	0.0683	benign	0.303	Stabilizing	0.006	N	0.153	neutral	N	0.425755934	None	None	I
H/P	0.2614	likely_benign	0.2746	benign	0.902	Stabilizing	0.028	N	0.313	neutral	D	0.522245118	None	None	I
H/Q	0.0736	likely_benign	0.0735	benign	0.397	Stabilizing	None	N	0.055	neutral	N	0.35764543	None	None	I
H/R	0.071	likely_benign	0.0695	benign	-0.243	Destabilizing	0.003	N	0.142	neutral	N	0.423966422	None	None	I
H/S	0.1017	likely_benign	0.1029	benign	0.43	Stabilizing	0.002	N	0.233	neutral	None	None	None	None	I
H/T	0.0971	likely_benign	0.0988	benign	0.546	Stabilizing	0.008	N	0.262	neutral	None	None	None	None	I
H/V	0.1031	likely_benign	0.1062	benign	0.902	Stabilizing	0.004	N	0.285	neutral	None	None	None	None	I
H/W	0.2846	likely_benign	0.2884	benign	0.999	Stabilizing	0.497	N	0.405	neutral	None	None	None	None	I
H/Y	0.0824	likely_benign	0.0849	benign	1.278	Stabilizing	0.028	N	0.339	neutral	N	0.492789002	None	None	I

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.