TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6432	19519;19520;19521	chr2:178728632;178728631;178728630	chr2:179593359;179593358;179593357
N2AB	6115	18568;18569;18570	chr2:178728632;178728631;178728630	chr2:179593359;179593358;179593357
N2A	5188	15787;15788;15789	chr2:178728632;178728631;178728630	chr2:179593359;179593358;179593357
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-48
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3092
• 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/L	None	None	0.015	N	0.431	0.231	0.618519337204	gnomAD-4.0.0	6.84443E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99627E-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
S/A	0.0891	likely_benign	0.0851	benign	-0.998	Destabilizing	None	N	0.151	neutral	N	0.505795585	None	None	N
S/C	0.1612	likely_benign	0.1425	benign	-0.841	Destabilizing	0.883	D	0.511	neutral	None	None	None	None	N
S/D	0.4125	ambiguous	0.3562	ambiguous	-0.963	Destabilizing	0.22	N	0.39	neutral	None	None	None	None	N
S/E	0.4848	ambiguous	0.4318	ambiguous	-0.871	Destabilizing	0.22	N	0.373	neutral	None	None	None	None	N
S/F	0.2067	likely_benign	0.1906	benign	-1.161	Destabilizing	0.497	N	0.536	neutral	None	None	None	None	N
S/G	0.104	likely_benign	0.0969	benign	-1.304	Destabilizing	0.055	N	0.362	neutral	None	None	None	None	N
S/H	0.2548	likely_benign	0.2435	benign	-1.742	Destabilizing	0.859	D	0.521	neutral	None	None	None	None	N
S/I	0.146	likely_benign	0.1407	benign	-0.262	Destabilizing	0.124	N	0.485	neutral	None	None	None	None	N
S/K	0.5222	ambiguous	0.4955	ambiguous	-0.488	Destabilizing	0.002	N	0.119	neutral	None	None	None	None	N
S/L	0.1053	likely_benign	0.0987	benign	-0.262	Destabilizing	0.015	N	0.431	neutral	N	0.513953708	None	None	N
S/M	0.1644	likely_benign	0.173	benign	-0.083	Destabilizing	0.009	N	0.36	neutral	None	None	None	None	N
S/N	0.1256	likely_benign	0.1168	benign	-0.834	Destabilizing	0.22	N	0.399	neutral	None	None	None	None	N
S/P	0.7246	likely_pathogenic	0.6483	pathogenic	-0.474	Destabilizing	0.301	N	0.477	neutral	N	0.510510758	None	None	N
S/Q	0.3773	ambiguous	0.3631	ambiguous	-0.876	Destabilizing	0.22	N	0.471	neutral	None	None	None	None	N
S/R	0.4157	ambiguous	0.3769	ambiguous	-0.585	Destabilizing	0.124	N	0.445	neutral	None	None	None	None	N
S/T	0.069	likely_benign	0.0704	benign	-0.72	Destabilizing	None	N	0.128	neutral	N	0.452809249	None	None	N
S/V	0.1545	likely_benign	0.1541	benign	-0.474	Destabilizing	0.055	N	0.447	neutral	None	None	None	None	N
S/W	0.3101	likely_benign	0.2913	benign	-1.192	Destabilizing	0.958	D	0.597	neutral	None	None	None	None	N
S/Y	0.1898	likely_benign	0.1669	benign	-0.842	Destabilizing	0.667	D	0.549	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.