TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8856	26791;26792;26793	chr2:178714092;178714091;178714090	chr2:179578819;179578818;179578817
N2AB	8539	25840;25841;25842	chr2:178714092;178714091;178714090	chr2:179578819;179578818;179578817
N2A	7612	23059;23060;23061	chr2:178714092;178714091;178714090	chr2:179578819;179578818;179578817
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-74
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5028
• 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
T/N	rs1331657608	None	0.982	N	0.509	0.34	0.540697301583	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1331657608	None	0.982	N	0.509	0.34	0.540697301583	gnomAD-4.0.0	6.57566E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47033E-05	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
T/A	0.1378	likely_benign	0.1507	benign	-0.248	Destabilizing	0.17	N	0.288	neutral	N	0.492076926	None	None	N
T/C	0.6388	likely_pathogenic	0.6649	pathogenic	-0.311	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	N
T/D	0.4197	ambiguous	0.4383	ambiguous	0.132	Stabilizing	0.986	D	0.491	neutral	None	None	None	None	N
T/E	0.3762	ambiguous	0.4159	ambiguous	0.064	Stabilizing	0.986	D	0.507	neutral	None	None	None	None	N
T/F	0.2198	likely_benign	0.221	benign	-0.741	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
T/G	0.3659	ambiguous	0.3954	ambiguous	-0.372	Destabilizing	0.91	D	0.588	neutral	None	None	None	None	N
T/H	0.2694	likely_benign	0.2915	benign	-0.51	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
T/I	0.234	likely_benign	0.2278	benign	-0.04	Destabilizing	0.991	D	0.531	neutral	N	0.498042893	None	None	N
T/K	0.2173	likely_benign	0.2563	benign	-0.335	Destabilizing	0.986	D	0.499	neutral	None	None	None	None	N
T/L	0.1347	likely_benign	0.1384	benign	-0.04	Destabilizing	0.953	D	0.528	neutral	None	None	None	None	N
T/M	0.0985	likely_benign	0.103	benign	-0.104	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
T/N	0.1215	likely_benign	0.1241	benign	-0.126	Destabilizing	0.982	D	0.509	neutral	N	0.466218477	None	None	N
T/P	0.3696	ambiguous	0.4503	ambiguous	-0.081	Destabilizing	0.991	D	0.535	neutral	N	0.491848529	None	None	N
T/Q	0.2666	likely_benign	0.3006	benign	-0.315	Destabilizing	0.993	D	0.536	neutral	None	None	None	None	N
T/R	0.2174	likely_benign	0.2498	benign	-0.02	Destabilizing	0.986	D	0.534	neutral	None	None	None	None	N
T/S	0.1074	likely_benign	0.1073	benign	-0.32	Destabilizing	0.17	N	0.337	neutral	N	0.434530133	None	None	N
T/V	0.2065	likely_benign	0.205	benign	-0.081	Destabilizing	0.953	D	0.498	neutral	None	None	None	None	N
T/W	0.6182	likely_pathogenic	0.6449	pathogenic	-0.799	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
T/Y	0.2584	likely_benign	0.2586	benign	-0.495	Destabilizing	0.998	D	0.654	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.