TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30904	92935;92936;92937	chr2:178548916;178548915;178548914	chr2:179413643;179413642;179413641
N2AB	29263	88012;88013;88014	chr2:178548916;178548915;178548914	chr2:179413643;179413642;179413641
N2A	28336	85231;85232;85233	chr2:178548916;178548915;178548914	chr2:179413643;179413642;179413641
N2B	21839	65740;65741;65742	chr2:178548916;178548915;178548914	chr2:179413643;179413642;179413641
Novex-1	21964	66115;66116;66117	chr2:178548916;178548915;178548914	chr2:179413643;179413642;179413641
Novex-2	22031	66316;66317;66318	chr2:178548916;178548915;178548914	chr2:179413643;179413642;179413641
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: Fn3-113
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.5669
• Predicted PPI site: I

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/E	rs370265204	0.476	0.046	N	0.265	0.161	None	gnomAD-2.1.1	2.85E-05	None	None	None	None	I	None	3.30579E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs370265204	0.476	0.046	N	0.265	0.161	None	gnomAD-3.1.2	7.88E-05	None	None	None	None	I	None	2.89394E-04	0	0	0	0	None	0	0	0	0	0
K/E	rs370265204	0.476	0.046	N	0.265	0.161	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
K/E	rs370265204	0.476	0.046	N	0.265	0.161	None	gnomAD-4.0.0	2.5404E-05	None	None	None	None	I	None	4.79616E-04	1.66617E-05	None	0	0	None	0	0	0	0	6.40184E-05

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	0.2544	likely_benign	0.2685	benign	-0.176	Destabilizing	0.919	D	0.609	neutral	None	None	None	None	I
K/C	0.56	ambiguous	0.577	pathogenic	-0.361	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
K/D	0.6367	likely_pathogenic	0.6336	pathogenic	0.354	Stabilizing	0.851	D	0.627	neutral	None	None	None	None	I
K/E	0.1451	likely_benign	0.1666	benign	0.398	Stabilizing	0.046	N	0.265	neutral	N	0.379681635	None	None	I
K/F	0.6362	likely_pathogenic	0.655	pathogenic	-0.241	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	I
K/G	0.4702	ambiguous	0.4956	ambiguous	-0.426	Destabilizing	0.959	D	0.724	prob.delet.	None	None	None	None	I
K/H	0.3295	likely_benign	0.3338	benign	-0.667	Destabilizing	0.988	D	0.701	prob.neutral	None	None	None	None	I
K/I	0.2209	likely_benign	0.2221	benign	0.415	Stabilizing	0.984	D	0.764	deleterious	N	0.396576672	None	None	I
K/L	0.249	likely_benign	0.2567	benign	0.415	Stabilizing	0.919	D	0.731	prob.delet.	None	None	None	None	I
K/M	0.1701	likely_benign	0.1716	benign	0.199	Stabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
K/N	0.4502	ambiguous	0.453	ambiguous	0.125	Stabilizing	0.896	D	0.647	neutral	N	0.446522703	None	None	I
K/P	0.4695	ambiguous	0.4816	ambiguous	0.248	Stabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	I
K/Q	0.1239	likely_benign	0.1304	benign	-0.009	Destabilizing	0.437	N	0.301	neutral	N	0.39272829	None	None	I
K/R	0.0809	likely_benign	0.0809	benign	-0.074	Destabilizing	0.026	N	0.301	neutral	N	0.400521054	None	None	I
K/S	0.3826	ambiguous	0.4045	ambiguous	-0.501	Destabilizing	0.919	D	0.598	neutral	None	None	None	None	I
K/T	0.1533	likely_benign	0.1567	benign	-0.28	Destabilizing	0.946	D	0.69	prob.neutral	N	0.394075085	None	None	I
K/V	0.2148	likely_benign	0.2162	benign	0.248	Stabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	I
K/W	0.6779	likely_pathogenic	0.6884	pathogenic	-0.179	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	I
K/Y	0.5294	ambiguous	0.5441	ambiguous	0.157	Stabilizing	0.996	D	0.761	deleterious	None	None	None	None	I

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.