TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9084	27475;27476;27477	chr2:178712775;178712774;178712773	chr2:179577502;179577501;179577500
N2AB	8767	26524;26525;26526	chr2:178712775;178712774;178712773	chr2:179577502;179577501;179577500
N2A	7840	23743;23744;23745	chr2:178712775;178712774;178712773	chr2:179577502;179577501;179577500
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-76
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4501
• 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	rs761372985	0.054	None	N	0.095	0.077	0.0762999501168	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
S/T	rs761372985	0.054	None	N	0.095	0.077	0.0762999501168	gnomAD-4.0.0	3.42109E-06	None	None	None	None	N	None	0	6.71021E-05	None	0	0	None	0	0	8.99465E-07	0	1.65656E-05

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	0.0731	likely_benign	0.072	benign	-0.255	Destabilizing	0.005	N	0.226	neutral	N	0.508677522	None	None	N
S/C	0.151	likely_benign	0.1529	benign	-0.211	Destabilizing	0.676	D	0.331	neutral	None	None	None	None	N
S/D	0.2073	likely_benign	0.2184	benign	0.116	Stabilizing	0.072	N	0.183	neutral	None	None	None	None	N
S/E	0.2639	likely_benign	0.2762	benign	0.003	Stabilizing	0.072	N	0.189	neutral	None	None	None	None	N
S/F	0.123	likely_benign	0.1209	benign	-1.011	Destabilizing	0.12	N	0.399	neutral	None	None	None	None	N
S/G	0.0951	likely_benign	0.0916	benign	-0.297	Destabilizing	0.031	N	0.174	neutral	None	None	None	None	N
S/H	0.2132	likely_benign	0.2188	benign	-0.719	Destabilizing	0.628	D	0.332	neutral	None	None	None	None	N
S/I	0.1222	likely_benign	0.1253	benign	-0.274	Destabilizing	0.016	N	0.301	neutral	None	None	None	None	N
S/K	0.3323	likely_benign	0.3446	ambiguous	-0.293	Destabilizing	0.072	N	0.186	neutral	None	None	None	None	N
S/L	0.0809	likely_benign	0.0779	benign	-0.274	Destabilizing	None	N	0.159	neutral	N	0.496596446	None	None	N
S/M	0.1558	likely_benign	0.1367	benign	-0.046	Destabilizing	0.214	N	0.343	neutral	None	None	None	None	N
S/N	0.1133	likely_benign	0.114	benign	-0.02	Destabilizing	0.072	N	0.295	neutral	None	None	None	None	N
S/P	0.2158	likely_benign	0.2323	benign	-0.244	Destabilizing	None	N	0.214	neutral	N	0.517339168	None	None	N
S/Q	0.2846	likely_benign	0.2889	benign	-0.274	Destabilizing	0.356	N	0.309	neutral	None	None	None	None	N
S/R	0.2768	likely_benign	0.293	benign	-0.078	Destabilizing	0.214	N	0.391	neutral	None	None	None	None	N
S/T	0.0779	likely_benign	0.0745	benign	-0.152	Destabilizing	None	N	0.095	neutral	N	0.503367703	None	None	N
S/V	0.1328	likely_benign	0.1298	benign	-0.244	Destabilizing	None	N	0.241	neutral	None	None	None	None	N
S/W	0.1972	likely_benign	0.2099	benign	-1.065	Destabilizing	0.864	D	0.381	neutral	None	None	None	None	N
S/Y	0.1253	likely_benign	0.128	benign	-0.758	Destabilizing	0.356	N	0.367	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.