TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9304	28135;28136;28137	chr2:178711326;178711325;178711324	chr2:179576053;179576052;179576051
N2AB	8987	27184;27185;27186	chr2:178711326;178711325;178711324	chr2:179576053;179576052;179576051
N2A	8060	24403;24404;24405	chr2:178711326;178711325;178711324	chr2:179576053;179576052;179576051
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-79
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4655
• 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	rs186512181	None	None	N	0.129	0.258	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
S/P	rs186512181	None	None	N	0.129	0.258	None	gnomAD-4.0.0	6.56418E-06	None	None	None	None	N	None	0	0	None	0	1.92901E-04	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
S/A	0.0971	likely_benign	0.0819	benign	-0.417	Destabilizing	0.001	N	0.091	neutral	N	0.428848514	None	None	N
S/C	0.1808	likely_benign	0.1726	benign	-0.275	Destabilizing	0.921	D	0.287	neutral	N	0.477986651	None	None	N
S/D	0.3892	ambiguous	0.4013	ambiguous	0.218	Stabilizing	0.418	N	0.095	neutral	None	None	None	None	N
S/E	0.439	ambiguous	0.4528	ambiguous	0.129	Stabilizing	0.228	N	0.103	neutral	None	None	None	None	N
S/F	0.1992	likely_benign	0.1684	benign	-0.998	Destabilizing	0.794	D	0.351	neutral	N	0.476972693	None	None	N
S/G	0.1257	likely_benign	0.1143	benign	-0.536	Destabilizing	0.129	N	0.145	neutral	None	None	None	None	N
S/H	0.2452	likely_benign	0.2627	benign	-1.054	Destabilizing	0.94	D	0.289	neutral	None	None	None	None	N
S/I	0.1435	likely_benign	0.1285	benign	-0.235	Destabilizing	0.264	N	0.229	neutral	None	None	None	None	N
S/K	0.439	ambiguous	0.483	ambiguous	-0.439	Destabilizing	0.228	N	0.102	neutral	None	None	None	None	N
S/L	0.0998	likely_benign	0.0846	benign	-0.235	Destabilizing	0.129	N	0.203	neutral	None	None	None	None	N
S/M	0.2301	likely_benign	0.21	benign	0.057	Stabilizing	0.836	D	0.29	neutral	None	None	None	None	N
S/N	0.1471	likely_benign	0.1428	benign	-0.186	Destabilizing	0.418	N	0.129	neutral	None	None	None	None	N
S/P	0.1554	likely_benign	0.1712	benign	-0.266	Destabilizing	None	N	0.129	neutral	N	0.491494483	None	None	N
S/Q	0.3456	ambiguous	0.3693	ambiguous	-0.44	Destabilizing	0.593	D	0.238	neutral	None	None	None	None	N
S/R	0.3279	likely_benign	0.3625	ambiguous	-0.248	Destabilizing	0.418	N	0.327	neutral	None	None	None	None	N
S/T	0.0981	likely_benign	0.0771	benign	-0.31	Destabilizing	None	N	0.077	neutral	N	0.374147238	None	None	N
S/V	0.1734	likely_benign	0.1435	benign	-0.266	Destabilizing	0.004	N	0.173	neutral	None	None	None	None	N
S/W	0.3249	likely_benign	0.3313	benign	-0.987	Destabilizing	0.983	D	0.302	neutral	None	None	None	None	N
S/Y	0.1813	likely_benign	0.1629	benign	-0.708	Destabilizing	0.921	D	0.332	neutral	N	0.465869877	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.