TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4963	15112;15113;15114	chr2:178735559;178735558;178735557	chr2:179600286;179600285;179600284
N2AB	4646	14161;14162;14163	chr2:178735559;178735558;178735557	chr2:179600286;179600285;179600284
N2A	3719	11380;11381;11382	chr2:178735559;178735558;178735557	chr2:179600286;179600285;179600284
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-32
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2682
• 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	rs754692297	-0.462	0.966	D	0.46	0.413	0.480274617672	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.44E-05	None	0	0	0
S/P	rs754692297	-0.462	0.966	D	0.46	0.413	0.480274617672	gnomAD-4.0.0	4.81869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.39947E-05	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	0.0771	likely_benign	0.0828	benign	-0.52	Destabilizing	0.022	N	0.139	neutral	N	0.506584706	None	None	N
S/C	0.129	likely_benign	0.1464	benign	-0.517	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
S/D	0.4128	ambiguous	0.525	ambiguous	-0.989	Destabilizing	0.842	D	0.486	neutral	None	None	None	None	N
S/E	0.4517	ambiguous	0.5324	ambiguous	-1.046	Destabilizing	0.842	D	0.443	neutral	None	None	None	None	N
S/F	0.1467	likely_benign	0.1703	benign	-1.256	Destabilizing	0.974	D	0.585	neutral	None	None	None	None	N
S/G	0.1067	likely_benign	0.1271	benign	-0.631	Destabilizing	0.525	D	0.399	neutral	None	None	None	None	N
S/H	0.3165	likely_benign	0.3689	ambiguous	-1.303	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
S/I	0.16	likely_benign	0.1902	benign	-0.34	Destabilizing	0.949	D	0.561	neutral	None	None	None	None	N
S/K	0.5548	ambiguous	0.6373	pathogenic	-0.511	Destabilizing	0.842	D	0.438	neutral	None	None	None	None	N
S/L	0.0944	likely_benign	0.105	benign	-0.34	Destabilizing	0.669	D	0.547	neutral	D	0.528796776	None	None	N
S/M	0.2045	likely_benign	0.2279	benign	0.173	Stabilizing	0.991	D	0.482	neutral	None	None	None	None	N
S/N	0.1462	likely_benign	0.1868	benign	-0.521	Destabilizing	0.842	D	0.505	neutral	None	None	None	None	N
S/P	0.863	likely_pathogenic	0.9142	pathogenic	-0.375	Destabilizing	0.966	D	0.46	neutral	D	0.667477474	None	None	N
S/Q	0.4214	ambiguous	0.4841	ambiguous	-0.921	Destabilizing	0.974	D	0.499	neutral	None	None	None	None	N
S/R	0.4326	ambiguous	0.5107	ambiguous	-0.262	Destabilizing	0.949	D	0.471	neutral	None	None	None	None	N
S/T	0.0775	likely_benign	0.0833	benign	-0.481	Destabilizing	0.022	N	0.13	neutral	N	0.468752858	None	None	N
S/V	0.1571	likely_benign	0.1819	benign	-0.375	Destabilizing	0.728	D	0.55	neutral	None	None	None	None	N
S/W	0.2957	likely_benign	0.3311	benign	-1.262	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
S/Y	0.1731	likely_benign	0.2003	benign	-0.924	Destabilizing	0.991	D	0.576	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.