TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33021	99286;99287;99288	chr2:178538768;178538767;178538766	chr2:179403495;179403494;179403493
N2AB	31380	94363;94364;94365	chr2:178538768;178538767;178538766	chr2:179403495;179403494;179403493
N2A	30453	91582;91583;91584	chr2:178538768;178538767;178538766	chr2:179403495;179403494;179403493
N2B	23956	72091;72092;72093	chr2:178538768;178538767;178538766	chr2:179403495;179403494;179403493
Novex-1	24081	72466;72467;72468	chr2:178538768;178538767;178538766	chr2:179403495;179403494;179403493
Novex-2	24148	72667;72668;72669	chr2:178538768;178538767;178538766	chr2:179403495;179403494;179403493
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-129
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6878
• 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/R	rs749757136	-0.195	0.011	N	0.251	0.104	0.253205268125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/R	rs749757136	-0.195	0.011	N	0.251	0.104	0.253205268125	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs749757136	-0.195	0.011	N	0.251	0.104	0.253205268125	gnomAD-4.0.0	2.54085E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.47535E-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
K/A	0.2945	likely_benign	0.3348	benign	-0.097	Destabilizing	0.919	D	0.625	neutral	None	None	None	None	N
K/C	0.6691	likely_pathogenic	0.702	pathogenic	-0.415	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/D	0.5778	likely_pathogenic	0.6259	pathogenic	-0.089	Destabilizing	0.988	D	0.644	neutral	None	None	None	None	N
K/E	0.2241	likely_benign	0.2399	benign	-0.022	Destabilizing	0.896	D	0.631	neutral	N	0.48981212	None	None	N
K/F	0.7496	likely_pathogenic	0.7864	pathogenic	-0.088	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	N
K/G	0.407	ambiguous	0.4689	ambiguous	-0.362	Destabilizing	0.959	D	0.596	neutral	None	None	None	None	N
K/H	0.336	likely_benign	0.3771	ambiguous	-0.557	Destabilizing	0.988	D	0.697	prob.neutral	None	None	None	None	N
K/I	0.3451	ambiguous	0.3621	ambiguous	0.545	Stabilizing	0.984	D	0.737	prob.delet.	N	0.489143871	None	None	N
K/L	0.3266	likely_benign	0.3637	ambiguous	0.545	Stabilizing	0.919	D	0.596	neutral	None	None	None	None	N
K/M	0.223	likely_benign	0.2485	benign	0.071	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
K/N	0.3961	ambiguous	0.4443	ambiguous	-0.127	Destabilizing	0.896	D	0.572	neutral	N	0.473027853	None	None	N
K/P	0.3995	ambiguous	0.4528	ambiguous	0.36	Stabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
K/Q	0.1408	likely_benign	0.1601	benign	-0.156	Destabilizing	0.896	D	0.597	neutral	N	0.501895983	None	None	N
K/R	0.0879	likely_benign	0.0932	benign	-0.229	Destabilizing	0.011	N	0.251	neutral	N	0.44454119	None	None	N
K/S	0.3949	ambiguous	0.445	ambiguous	-0.573	Destabilizing	0.919	D	0.563	neutral	None	None	None	None	N
K/T	0.2006	likely_benign	0.223	benign	-0.33	Destabilizing	0.946	D	0.622	neutral	N	0.469469454	None	None	N
K/V	0.3301	likely_benign	0.356	ambiguous	0.36	Stabilizing	0.988	D	0.637	neutral	None	None	None	None	N
K/W	0.7528	likely_pathogenic	0.7977	pathogenic	-0.134	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/Y	0.5977	likely_pathogenic	0.6279	pathogenic	0.202	Stabilizing	0.996	D	0.728	prob.delet.	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.