TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14710	44353;44354;44355	chr2:178630830;178630829;178630828	chr2:179495557;179495556;179495555
N2AB	13069	39430;39431;39432	chr2:178630830;178630829;178630828	chr2:179495557;179495556;179495555
N2A	12142	36649;36650;36651	chr2:178630830;178630829;178630828	chr2:179495557;179495556;179495555
N2B	5645	17158;17159;17160	chr2:178630830;178630829;178630828	chr2:179495557;179495556;179495555
Novex-1	5770	17533;17534;17535	chr2:178630830;178630829;178630828	chr2:179495557;179495556;179495555
Novex-2	5837	17734;17735;17736	chr2:178630830;178630829;178630828	chr2:179495557;179495556;179495555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-98
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.36
• 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
K/N	None	None	0.999	N	0.637	0.171	0.128392430309	gnomAD-4.0.0	6.84456E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99747E-07	0	0
K/Q	None	None	0.997	N	0.639	0.284	0.223146558224	gnomAD-4.0.0	2.05388E-06	None	None	None	None	N	None	0	2.23694E-05	None	0	0	None	0	0	1.80003E-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
K/A	0.5804	likely_pathogenic	0.7423	pathogenic	-0.031	Destabilizing	0.997	D	0.54	neutral	None	None	None	None	N
K/C	0.744	likely_pathogenic	0.8423	pathogenic	-0.236	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.6795	likely_pathogenic	0.8141	pathogenic	0.288	Stabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
K/E	0.3907	ambiguous	0.5715	pathogenic	0.298	Stabilizing	0.991	D	0.499	neutral	N	0.511789073	None	None	N
K/F	0.9095	likely_pathogenic	0.9565	pathogenic	-0.26	Destabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	N
K/G	0.5125	ambiguous	0.6598	pathogenic	-0.233	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
K/H	0.3948	ambiguous	0.5037	ambiguous	-0.567	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
K/I	0.8036	likely_pathogenic	0.9059	pathogenic	0.418	Stabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
K/L	0.6304	likely_pathogenic	0.7478	pathogenic	0.418	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	N
K/M	0.4815	ambiguous	0.6176	pathogenic	0.256	Stabilizing	1.0	D	0.654	prob.neutral	N	0.517682384	None	None	N
K/N	0.4825	ambiguous	0.6108	pathogenic	0.261	Stabilizing	0.999	D	0.637	neutral	N	0.410884909	None	None	N
K/P	0.9362	likely_pathogenic	0.9722	pathogenic	0.297	Stabilizing	1.0	D	0.722	deleterious	None	None	None	None	N
K/Q	0.2091	likely_benign	0.2948	benign	0.081	Stabilizing	0.997	D	0.639	neutral	N	0.421211686	None	None	N
K/R	0.0851	likely_benign	0.0957	benign	-0.022	Destabilizing	0.451	N	0.259	neutral	N	0.515050768	None	None	N
K/S	0.6203	likely_pathogenic	0.7711	pathogenic	-0.288	Destabilizing	0.997	D	0.581	neutral	None	None	None	None	N
K/T	0.571	likely_pathogenic	0.7632	pathogenic	-0.125	Destabilizing	0.999	D	0.683	prob.neutral	N	0.51568959	None	None	N
K/V	0.7625	likely_pathogenic	0.8795	pathogenic	0.297	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
K/W	0.8492	likely_pathogenic	0.9221	pathogenic	-0.248	Destabilizing	1.0	D	0.7	prob.delet.	None	None	None	None	N
K/Y	0.7405	likely_pathogenic	0.8503	pathogenic	0.119	Stabilizing	1.0	D	0.677	prob.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.