TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6068	18427;18428;18429	chr2:178730198;178730197;178730196	chr2:179594925;179594924;179594923
N2AB	5751	17476;17477;17478	chr2:178730198;178730197;178730196	chr2:179594925;179594924;179594923
N2A	4824	14695;14696;14697	chr2:178730198;178730197;178730196	chr2:179594925;179594924;179594923
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-44
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1699
• 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/T	None	None	0.012	N	0.363	0.119	0.0884992946249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0764	likely_benign	0.0715	benign	-0.903	Destabilizing	0.007	N	0.362	neutral	None	None	None	None	N
S/C	0.1214	likely_benign	0.1118	benign	-0.519	Destabilizing	0.295	N	0.623	neutral	N	0.500130643	None	None	N
S/D	0.3674	ambiguous	0.4039	ambiguous	-1.384	Destabilizing	0.136	N	0.513	neutral	None	None	None	None	N
S/E	0.3309	likely_benign	0.3573	ambiguous	-1.172	Destabilizing	0.136	N	0.455	neutral	None	None	None	None	N
S/F	0.0891	likely_benign	0.0958	benign	-0.678	Destabilizing	0.072	N	0.638	neutral	None	None	None	None	N
S/G	0.1387	likely_benign	0.128	benign	-1.306	Destabilizing	0.047	N	0.405	neutral	N	0.495749323	None	None	N
S/H	0.2	likely_benign	0.2086	benign	-1.577	Destabilizing	0.628	D	0.633	neutral	None	None	None	None	N
S/I	0.0392	likely_benign	0.0437	benign	0.132	Stabilizing	None	N	0.409	neutral	N	0.490406952	None	None	N
S/K	0.3906	ambiguous	0.4287	ambiguous	-0.105	Destabilizing	0.072	N	0.425	neutral	None	None	None	None	N
S/L	0.061	likely_benign	0.0628	benign	0.132	Stabilizing	None	N	0.417	neutral	None	None	None	None	N
S/M	0.0751	likely_benign	0.0798	benign	0.005	Stabilizing	0.003	N	0.416	neutral	None	None	None	None	N
S/N	0.1083	likely_benign	0.1168	benign	-0.817	Destabilizing	0.106	N	0.519	neutral	N	0.503636135	None	None	N
S/P	0.7769	likely_pathogenic	0.7899	pathogenic	-0.18	Destabilizing	0.325	N	0.656	neutral	None	None	None	None	N
S/Q	0.2892	likely_benign	0.3058	benign	-0.531	Destabilizing	0.136	N	0.543	neutral	None	None	None	None	N
S/R	0.296	likely_benign	0.3184	benign	-0.565	Destabilizing	0.106	N	0.669	neutral	N	0.502368687	None	None	N
S/T	0.06	likely_benign	0.0627	benign	-0.488	Destabilizing	0.012	N	0.363	neutral	N	0.478336838	None	None	N
S/V	0.0514	likely_benign	0.0548	benign	-0.18	Destabilizing	None	N	0.399	neutral	None	None	None	None	N
S/W	0.251	likely_benign	0.2433	benign	-0.954	Destabilizing	0.864	D	0.654	neutral	None	None	None	None	N
S/Y	0.1243	likely_benign	0.1224	benign	-0.5	Destabilizing	0.136	N	0.672	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.