TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21866	65821;65822;65823	chr2:178583207;178583206;178583205	chr2:179447934;179447933;179447932
N2AB	20225	60898;60899;60900	chr2:178583207;178583206;178583205	chr2:179447934;179447933;179447932
N2A	19298	58117;58118;58119	chr2:178583207;178583206;178583205	chr2:179447934;179447933;179447932
N2B	12801	38626;38627;38628	chr2:178583207;178583206;178583205	chr2:179447934;179447933;179447932
Novex-1	12926	39001;39002;39003	chr2:178583207;178583206;178583205	chr2:179447934;179447933;179447932
Novex-2	12993	39202;39203;39204	chr2:178583207;178583206;178583205	chr2:179447934;179447933;179447932
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-125
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3294
• 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/I	None	None	0.939	N	0.41	0.327	0.73638873623	gnomAD-4.0.0	6.87581E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66423E-05
S/N	rs2048167359	None	0.521	N	0.286	0.108	0.222439326576	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs2048167359	None	0.521	N	0.286	0.108	0.222439326576	gnomAD-4.0.0	3.73501E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.10437E-06	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	0.135	likely_benign	0.1295	benign	-0.105	Destabilizing	0.373	N	0.306	neutral	None	None	None	None	N
S/C	0.2492	likely_benign	0.1998	benign	-0.217	Destabilizing	0.994	D	0.369	neutral	N	0.496944028	None	None	N
S/D	0.3189	likely_benign	0.2526	benign	0.043	Stabilizing	0.004	N	0.125	neutral	None	None	None	None	N
S/E	0.6407	likely_pathogenic	0.5609	ambiguous	-0.058	Destabilizing	0.373	N	0.277	neutral	None	None	None	None	N
S/F	0.6873	likely_pathogenic	0.6259	pathogenic	-0.762	Destabilizing	0.984	D	0.385	neutral	None	None	None	None	N
S/G	0.0787	likely_benign	0.073	benign	-0.191	Destabilizing	0.001	N	0.116	neutral	N	0.495903878	None	None	N
S/H	0.5223	ambiguous	0.4449	ambiguous	-0.622	Destabilizing	0.984	D	0.356	neutral	None	None	None	None	N
S/I	0.5517	ambiguous	0.4682	ambiguous	-0.014	Destabilizing	0.939	D	0.41	neutral	N	0.496597312	None	None	N
S/K	0.7857	likely_pathogenic	0.7194	pathogenic	-0.42	Destabilizing	0.742	D	0.249	neutral	None	None	None	None	N
S/L	0.2745	likely_benign	0.2427	benign	-0.014	Destabilizing	0.854	D	0.333	neutral	None	None	None	None	N
S/M	0.4493	ambiguous	0.4152	ambiguous	0.037	Stabilizing	0.996	D	0.353	neutral	None	None	None	None	N
S/N	0.1504	likely_benign	0.1204	benign	-0.097	Destabilizing	0.521	D	0.286	neutral	N	0.495210445	None	None	N
S/P	0.1632	likely_benign	0.1444	benign	-0.017	Destabilizing	0.953	D	0.379	neutral	None	None	None	None	N
S/Q	0.6658	likely_pathogenic	0.5965	pathogenic	-0.329	Destabilizing	0.953	D	0.366	neutral	None	None	None	None	N
S/R	0.7624	likely_pathogenic	0.6767	pathogenic	-0.186	Destabilizing	0.939	D	0.381	neutral	N	0.49573052	None	None	N
S/T	0.1075	likely_benign	0.1043	benign	-0.181	Destabilizing	0.684	D	0.288	neutral	N	0.476798043	None	None	N
S/V	0.48	ambiguous	0.4163	ambiguous	-0.017	Destabilizing	0.953	D	0.373	neutral	None	None	None	None	N
S/W	0.7552	likely_pathogenic	0.7142	pathogenic	-0.851	Destabilizing	0.996	D	0.491	neutral	None	None	None	None	N
S/Y	0.564	ambiguous	0.5061	ambiguous	-0.535	Destabilizing	0.984	D	0.382	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.