TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14095	42508;42509;42510	chr2:178634498;178634497;178634496	chr2:179499225;179499224;179499223
N2AB	12454	37585;37586;37587	chr2:178634498;178634497;178634496	chr2:179499225;179499224;179499223
N2A	11527	34804;34805;34806	chr2:178634498;178634497;178634496	chr2:179499225;179499224;179499223
N2B	5030	15313;15314;15315	chr2:178634498;178634497;178634496	chr2:179499225;179499224;179499223
Novex-1	5155	15688;15689;15690	chr2:178634498;178634497;178634496	chr2:179499225;179499224;179499223
Novex-2	5222	15889;15890;15891	chr2:178634498;178634497;178634496	chr2:179499225;179499224;179499223
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-91
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.2608
• 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/F	rs762662244	-1.187	0.989	D	0.447	0.346	0.505518066752	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
S/F	rs762662244	-1.187	0.989	D	0.447	0.346	0.505518066752	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	2.77639E-05	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	0.2295	likely_benign	0.2538	benign	-0.537	Destabilizing	0.454	N	0.366	neutral	N	0.508243773	None	None	N
S/C	0.2163	likely_benign	0.2193	benign	-0.345	Destabilizing	0.997	D	0.363	neutral	D	0.522729845	None	None	N
S/D	0.5797	likely_pathogenic	0.5959	pathogenic	0.299	Stabilizing	0.007	N	0.144	neutral	None	None	None	None	N
S/E	0.8879	likely_pathogenic	0.8834	pathogenic	0.222	Stabilizing	0.525	D	0.338	neutral	None	None	None	None	N
S/F	0.8028	likely_pathogenic	0.8226	pathogenic	-1.132	Destabilizing	0.989	D	0.447	neutral	D	0.615889607	None	None	N
S/G	0.0871	likely_benign	0.0904	benign	-0.661	Destabilizing	0.002	N	0.133	neutral	None	None	None	None	N
S/H	0.7209	likely_pathogenic	0.6924	pathogenic	-1.117	Destabilizing	0.991	D	0.338	neutral	None	None	None	None	N
S/I	0.7396	likely_pathogenic	0.7491	pathogenic	-0.337	Destabilizing	0.991	D	0.467	neutral	None	None	None	None	N
S/K	0.9362	likely_pathogenic	0.9288	pathogenic	-0.445	Destabilizing	0.842	D	0.324	neutral	None	None	None	None	N
S/L	0.4288	ambiguous	0.4473	ambiguous	-0.337	Destabilizing	0.915	D	0.445	neutral	None	None	None	None	N
S/M	0.6209	likely_pathogenic	0.6288	pathogenic	-0.134	Destabilizing	0.998	D	0.341	neutral	None	None	None	None	N
S/N	0.249	likely_benign	0.2425	benign	-0.229	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	N
S/P	0.8984	likely_pathogenic	0.9225	pathogenic	-0.375	Destabilizing	0.989	D	0.366	neutral	D	0.614010819	None	None	N
S/Q	0.8626	likely_pathogenic	0.8471	pathogenic	-0.421	Destabilizing	0.974	D	0.382	neutral	None	None	None	None	N
S/R	0.8885	likely_pathogenic	0.8848	pathogenic	-0.274	Destabilizing	0.974	D	0.375	neutral	None	None	None	None	N
S/T	0.1321	likely_benign	0.1391	benign	-0.334	Destabilizing	0.891	D	0.366	neutral	N	0.471534802	None	None	N
S/V	0.6787	likely_pathogenic	0.7005	pathogenic	-0.375	Destabilizing	0.974	D	0.469	neutral	None	None	None	None	N
S/W	0.8372	likely_pathogenic	0.8396	pathogenic	-1.13	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
S/Y	0.719	likely_pathogenic	0.7161	pathogenic	-0.848	Destabilizing	0.989	D	0.443	neutral	D	0.575677048	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.