TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20319	61180;61181;61182	chr2:178590770;178590769;178590768	chr2:179455497;179455496;179455495
N2AB	18678	56257;56258;56259	chr2:178590770;178590769;178590768	chr2:179455497;179455496;179455495
N2A	17751	53476;53477;53478	chr2:178590770;178590769;178590768	chr2:179455497;179455496;179455495
N2B	11254	33985;33986;33987	chr2:178590770;178590769;178590768	chr2:179455497;179455496;179455495
Novex-1	11379	34360;34361;34362	chr2:178590770;178590769;178590768	chr2:179455497;179455496;179455495
Novex-2	11446	34561;34562;34563	chr2:178590770;178590769;178590768	chr2:179455497;179455496;179455495
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-35
• Domain position: 49
• Structural Position: 67
• Q(SASA): 0.2973
• 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
R/S	None	None	1.0	N	0.775	0.32	0.265010934533	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
R/A	0.7147	likely_pathogenic	0.7309	pathogenic	-0.791	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
R/C	0.2947	likely_benign	0.3171	benign	-0.854	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
R/D	0.9491	likely_pathogenic	0.9503	pathogenic	0.029	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
R/E	0.7603	likely_pathogenic	0.7719	pathogenic	0.194	Stabilizing	0.999	D	0.665	neutral	None	None	None	None	N
R/F	0.8255	likely_pathogenic	0.8233	pathogenic	-0.395	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
R/G	0.7203	likely_pathogenic	0.7277	pathogenic	-1.131	Destabilizing	1.0	D	0.715	prob.delet.	N	0.488992514	None	None	N
R/H	0.22	likely_benign	0.2328	benign	-1.288	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
R/I	0.5353	ambiguous	0.5385	ambiguous	0.136	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
R/K	0.1593	likely_benign	0.1598	benign	-0.676	Destabilizing	0.997	D	0.512	neutral	N	0.424339277	None	None	N
R/L	0.4108	ambiguous	0.4085	ambiguous	0.136	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/M	0.4909	ambiguous	0.4938	ambiguous	-0.423	Destabilizing	1.0	D	0.795	deleterious	N	0.471141748	None	None	N
R/N	0.884	likely_pathogenic	0.8802	pathogenic	-0.396	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/P	0.611	likely_pathogenic	0.642	pathogenic	-0.153	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
R/Q	0.1838	likely_benign	0.1926	benign	-0.421	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
R/S	0.8524	likely_pathogenic	0.8647	pathogenic	-1.157	Destabilizing	1.0	D	0.775	deleterious	N	0.499258323	None	None	N
R/T	0.5592	ambiguous	0.5813	pathogenic	-0.791	Destabilizing	1.0	D	0.768	deleterious	N	0.477805615	None	None	N
R/V	0.6044	likely_pathogenic	0.6109	pathogenic	-0.153	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
R/W	0.3617	ambiguous	0.375	ambiguous	-0.035	Destabilizing	1.0	D	0.764	deleterious	N	0.511616219	None	None	N
R/Y	0.6954	likely_pathogenic	0.7021	pathogenic	0.22	Stabilizing	1.0	D	0.779	deleterious	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.