TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20985	63178;63179;63180	chr2:178588772;178588771;178588770	chr2:179453499;179453498;179453497
N2AB	19344	58255;58256;58257	chr2:178588772;178588771;178588770	chr2:179453499;179453498;179453497
N2A	18417	55474;55475;55476	chr2:178588772;178588771;178588770	chr2:179453499;179453498;179453497
N2B	11920	35983;35984;35985	chr2:178588772;178588771;178588770	chr2:179453499;179453498;179453497
Novex-1	12045	36358;36359;36360	chr2:178588772;178588771;178588770	chr2:179453499;179453498;179453497
Novex-2	12112	36559;36560;36561	chr2:178588772;178588771;178588770	chr2:179453499;179453498;179453497
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-40
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5922
• 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
N/K	None	None	0.062	N	0.297	0.104	0.0846915920261	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
N/A	0.1541	likely_benign	0.222	benign	-0.742	Destabilizing	None	N	0.23	neutral	None	None	None	None	N
N/C	0.182	likely_benign	0.2394	benign	0.139	Stabilizing	0.824	D	0.461	neutral	None	None	None	None	N
N/D	0.2184	likely_benign	0.2252	benign	-0.46	Destabilizing	0.117	N	0.311	neutral	N	0.420778896	None	None	N
N/E	0.3194	likely_benign	0.3464	ambiguous	-0.387	Destabilizing	0.081	N	0.299	neutral	None	None	None	None	N
N/F	0.3807	ambiguous	0.4758	ambiguous	-0.541	Destabilizing	0.555	D	0.492	neutral	None	None	None	None	N
N/G	0.2202	likely_benign	0.2521	benign	-1.064	Destabilizing	0.035	N	0.309	neutral	None	None	None	None	N
N/H	0.115	likely_benign	0.1257	benign	-0.947	Destabilizing	0.484	N	0.463	neutral	N	0.474864097	None	None	N
N/I	0.1683	likely_benign	0.2194	benign	0.069	Stabilizing	0.188	N	0.503	neutral	N	0.445061265	None	None	N
N/K	0.2565	likely_benign	0.2659	benign	-0.402	Destabilizing	0.062	N	0.297	neutral	N	0.361287876	None	None	N
N/L	0.1489	likely_benign	0.1983	benign	0.069	Stabilizing	0.081	N	0.443	neutral	None	None	None	None	N
N/M	0.1994	likely_benign	0.271	benign	0.434	Stabilizing	0.555	D	0.441	neutral	None	None	None	None	N
N/P	0.5506	ambiguous	0.6658	pathogenic	-0.172	Destabilizing	0.38	N	0.483	neutral	None	None	None	None	N
N/Q	0.2474	likely_benign	0.2897	benign	-0.788	Destabilizing	0.38	N	0.451	neutral	None	None	None	None	N
N/R	0.3127	likely_benign	0.3491	ambiguous	-0.481	Destabilizing	0.149	N	0.418	neutral	None	None	None	None	N
N/S	0.0934	likely_benign	0.1104	benign	-0.776	Destabilizing	None	N	0.145	neutral	N	0.373523667	None	None	N
N/T	0.1196	likely_benign	0.1583	benign	-0.526	Destabilizing	None	N	0.147	neutral	N	0.397477962	None	None	N
N/V	0.1759	likely_benign	0.2494	benign	-0.172	Destabilizing	0.081	N	0.435	neutral	None	None	None	None	N
N/W	0.6279	likely_pathogenic	0.7025	pathogenic	-0.387	Destabilizing	0.935	D	0.541	neutral	None	None	None	None	N
N/Y	0.1416	likely_benign	0.1531	benign	-0.196	Destabilizing	0.484	N	0.465	neutral	N	0.450256441	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.