TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5375	16348;16349;16350	chr2:178733053;178733052;178733051	chr2:179597780;179597779;179597778
N2AB	5058	15397;15398;15399	chr2:178733053;178733052;178733051	chr2:179597780;179597779;179597778
N2A	4131	12616;12617;12618	chr2:178733053;178733052;178733051	chr2:179597780;179597779;179597778
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-37
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3931
• 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	0.009	N	0.381	0.219	0.112648838833	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.2847	likely_benign	0.2723	benign	-0.494	Destabilizing	0.129	N	0.453	neutral	None	None	None	None	N
R/C	0.1209	likely_benign	0.1162	benign	-0.438	Destabilizing	0.983	D	0.495	neutral	None	None	None	None	N
R/D	0.5043	ambiguous	0.4784	ambiguous	-0.068	Destabilizing	0.418	N	0.512	neutral	None	None	None	None	N
R/E	0.3077	likely_benign	0.2925	benign	0.016	Stabilizing	0.129	N	0.503	neutral	None	None	None	None	N
R/F	0.3108	likely_benign	0.3041	benign	-0.59	Destabilizing	0.716	D	0.509	neutral	None	None	None	None	N
R/G	0.2082	likely_benign	0.1982	benign	-0.746	Destabilizing	0.183	N	0.486	neutral	N	0.457351182	None	None	N
R/H	0.0706	likely_benign	0.068	benign	-1.171	Destabilizing	0.002	N	0.429	neutral	None	None	None	None	N
R/I	0.182	likely_benign	0.172	benign	0.156	Stabilizing	0.794	D	0.536	neutral	N	0.454341605	None	None	N
R/K	0.1122	likely_benign	0.1101	benign	-0.518	Destabilizing	0.001	N	0.307	neutral	N	0.421037108	None	None	N
R/L	0.1553	likely_benign	0.1504	benign	0.156	Stabilizing	0.418	N	0.512	neutral	None	None	None	None	N
R/M	0.24	likely_benign	0.2308	benign	-0.097	Destabilizing	0.94	D	0.519	neutral	None	None	None	None	N
R/N	0.3599	ambiguous	0.337	benign	-0.008	Destabilizing	0.264	N	0.501	neutral	None	None	None	None	N
R/P	0.6397	likely_pathogenic	0.6259	pathogenic	-0.039	Destabilizing	0.593	D	0.543	neutral	None	None	None	None	N
R/Q	0.0875	likely_benign	0.0853	benign	-0.223	Destabilizing	0.027	N	0.433	neutral	None	None	None	None	N
R/S	0.2801	likely_benign	0.2619	benign	-0.636	Destabilizing	0.009	N	0.381	neutral	N	0.453341527	None	None	N
R/T	0.1714	likely_benign	0.1606	benign	-0.395	Destabilizing	0.101	N	0.507	neutral	N	0.400120331	None	None	N
R/V	0.2242	likely_benign	0.2174	benign	-0.039	Destabilizing	0.418	N	0.522	neutral	None	None	None	None	N
R/W	0.1429	likely_benign	0.139	benign	-0.402	Destabilizing	0.983	D	0.519	neutral	None	None	None	None	N
R/Y	0.2279	likely_benign	0.215	benign	-0.05	Destabilizing	0.557	D	0.541	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.