TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25445	76558;76559;76560	chr2:178569799;178569798;178569797	chr2:179434526;179434525;179434524
N2AB	23804	71635;71636;71637	chr2:178569799;178569798;178569797	chr2:179434526;179434525;179434524
N2A	22877	68854;68855;68856	chr2:178569799;178569798;178569797	chr2:179434526;179434525;179434524
N2B	16380	49363;49364;49365	chr2:178569799;178569798;178569797	chr2:179434526;179434525;179434524
Novex-1	16505	49738;49739;49740	chr2:178569799;178569798;178569797	chr2:179434526;179434525;179434524
Novex-2	16572	49939;49940;49941	chr2:178569799;178569798;178569797	chr2:179434526;179434525;179434524
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-73
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0767
• 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
C/Y	rs2154168053	None	0.99	N	0.727	0.381	0.686824916271	gnomAD-4.0.0	1.3003E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7092E-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
C/A	0.3063	likely_benign	0.282	benign	-1.519	Destabilizing	0.717	D	0.559	neutral	None	None	None	None	N
C/D	0.7337	likely_pathogenic	0.6739	pathogenic	-1.29	Destabilizing	0.956	D	0.759	deleterious	None	None	None	None	N
C/E	0.6711	likely_pathogenic	0.6296	pathogenic	-1.065	Destabilizing	0.915	D	0.751	deleterious	None	None	None	None	N
C/F	0.2755	likely_benign	0.2736	benign	-1.04	Destabilizing	0.99	D	0.727	prob.delet.	N	0.501837268	None	None	N
C/G	0.1813	likely_benign	0.1528	benign	-1.841	Destabilizing	0.942	D	0.751	deleterious	N	0.465822149	None	None	N
C/H	0.3751	ambiguous	0.3283	benign	-2.131	Highly Destabilizing	0.994	D	0.769	deleterious	None	None	None	None	N
C/I	0.5236	ambiguous	0.5337	ambiguous	-0.651	Destabilizing	0.978	D	0.667	neutral	None	None	None	None	N
C/K	0.4325	ambiguous	0.3702	ambiguous	-0.861	Destabilizing	0.915	D	0.751	deleterious	None	None	None	None	N
C/L	0.419	ambiguous	0.3937	ambiguous	-0.651	Destabilizing	0.86	D	0.597	neutral	None	None	None	None	N
C/M	0.4907	ambiguous	0.4819	ambiguous	-0.228	Destabilizing	0.994	D	0.683	prob.neutral	None	None	None	None	N
C/N	0.3973	ambiguous	0.3698	ambiguous	-1.363	Destabilizing	0.956	D	0.784	deleterious	None	None	None	None	N
C/P	0.9881	likely_pathogenic	0.9781	pathogenic	-0.92	Destabilizing	0.978	D	0.793	deleterious	None	None	None	None	N
C/Q	0.3126	likely_benign	0.2611	benign	-0.903	Destabilizing	0.16	N	0.538	neutral	None	None	None	None	N
C/R	0.1884	likely_benign	0.1548	benign	-1.366	Destabilizing	0.89	D	0.783	deleterious	N	0.415119574	None	None	N
C/S	0.2266	likely_benign	0.2165	benign	-1.631	Destabilizing	0.822	D	0.639	neutral	N	0.488001179	None	None	N
C/T	0.4059	ambiguous	0.3931	ambiguous	-1.237	Destabilizing	0.86	D	0.645	neutral	None	None	None	None	N
C/V	0.4411	ambiguous	0.4412	ambiguous	-0.92	Destabilizing	0.86	D	0.647	neutral	None	None	None	None	N
C/W	0.5384	ambiguous	0.5242	ambiguous	-1.46	Destabilizing	0.997	D	0.725	prob.delet.	N	0.49315907	None	None	N
C/Y	0.2623	likely_benign	0.2583	benign	-1.21	Destabilizing	0.99	D	0.727	prob.delet.	N	0.501490551	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.