TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9105	27538;27539;27540	chr2:178712712;178712711;178712710	chr2:179577439;179577438;179577437
N2AB	8788	26587;26588;26589	chr2:178712712;178712711;178712710	chr2:179577439;179577438;179577437
N2A	7861	23806;23807;23808	chr2:178712712;178712711;178712710	chr2:179577439;179577438;179577437
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: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-76
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3437
• 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
H/R	None	None	None	N	0.16	0.112	0.154104182512	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
H/Y	rs771109303	0.794	0.065	N	0.457	0.091	0.278968121808	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
H/Y	rs771109303	0.794	0.065	N	0.457	0.091	0.278968121808	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30873E-04	0	0	0	None	0	0	0	0	0
H/Y	rs771109303	0.794	0.065	N	0.457	0.091	0.278968121808	gnomAD-4.0.0	8.97128E-06	None	None	None	None	N	None	0	1.18628E-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
H/A	0.1999	likely_benign	0.1786	benign	-0.9	Destabilizing	0.004	N	0.347	neutral	None	None	None	None	N
H/C	0.2149	likely_benign	0.1909	benign	-0.041	Destabilizing	0.245	N	0.555	neutral	None	None	None	None	N
H/D	0.1634	likely_benign	0.1524	benign	-0.453	Destabilizing	None	N	0.161	neutral	N	0.504582077	None	None	N
H/E	0.2038	likely_benign	0.1919	benign	-0.328	Destabilizing	0.004	N	0.262	neutral	None	None	None	None	N
H/F	0.2876	likely_benign	0.2513	benign	0.521	Stabilizing	0.085	N	0.559	neutral	None	None	None	None	N
H/G	0.2651	likely_benign	0.2273	benign	-1.294	Destabilizing	0.004	N	0.384	neutral	None	None	None	None	N
H/I	0.2538	likely_benign	0.2334	benign	0.205	Stabilizing	0.022	N	0.588	neutral	None	None	None	None	N
H/K	0.1679	likely_benign	0.1625	benign	-0.507	Destabilizing	0.009	N	0.341	neutral	None	None	None	None	N
H/L	0.1101	likely_benign	0.1008	benign	0.205	Stabilizing	0.007	N	0.435	neutral	N	0.495693235	None	None	N
H/M	0.3714	ambiguous	0.3436	ambiguous	0.014	Stabilizing	0.245	N	0.554	neutral	None	None	None	None	N
H/N	0.0833	likely_benign	0.0772	benign	-0.714	Destabilizing	None	N	0.167	neutral	N	0.451902385	None	None	N
H/P	0.2348	likely_benign	0.2094	benign	-0.144	Destabilizing	0.065	N	0.602	neutral	D	0.52413063	None	None	N
H/Q	0.1178	likely_benign	0.1095	benign	-0.444	Destabilizing	None	N	0.146	neutral	N	0.463215457	None	None	N
H/R	0.0766	likely_benign	0.0728	benign	-0.971	Destabilizing	None	N	0.16	neutral	N	0.472989733	None	None	N
H/S	0.1552	likely_benign	0.1371	benign	-0.814	Destabilizing	None	N	0.163	neutral	None	None	None	None	N
H/T	0.171	likely_benign	0.1541	benign	-0.574	Destabilizing	None	N	0.255	neutral	None	None	None	None	N
H/V	0.1985	likely_benign	0.1792	benign	-0.144	Destabilizing	None	N	0.381	neutral	None	None	None	None	N
H/W	0.3314	likely_benign	0.313	benign	0.939	Stabilizing	0.788	D	0.549	neutral	None	None	None	None	N
H/Y	0.0978	likely_benign	0.0904	benign	0.947	Stabilizing	0.065	N	0.457	neutral	N	0.512009481	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.