TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31428	94507;94508;94509	chr2:178547243;178547242;178547241	chr2:179411970;179411969;179411968
N2AB	29787	89584;89585;89586	chr2:178547243;178547242;178547241	chr2:179411970;179411969;179411968
N2A	28860	86803;86804;86805	chr2:178547243;178547242;178547241	chr2:179411970;179411969;179411968
N2B	22363	67312;67313;67314	chr2:178547243;178547242;178547241	chr2:179411970;179411969;179411968
Novex-1	22488	67687;67688;67689	chr2:178547243;178547242;178547241	chr2:179411970;179411969;179411968
Novex-2	22555	67888;67889;67890	chr2:178547243;178547242;178547241	chr2:179411970;179411969;179411968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-117
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3477
• 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
R/C	rs190282707	-1.298	1.0	N	0.772	0.384	0.717641377234	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	0	2.83E-05	None	0	2.04939E-04	None	0	None	0	7.82E-06	1.40489E-04
R/C	rs190282707	-1.298	1.0	N	0.772	0.384	0.717641377234	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	4.83E-05	0	0	0	5.78258E-04	None	0	0	0	2.06868E-04	0
R/C	rs190282707	-1.298	1.0	N	0.772	0.384	0.717641377234	gnomAD-4.0.0	1.05344E-05	None	None	None	None	N	None	3.99936E-05	0	None	0	2.45164E-04	None	0	0	8.47646E-07	1.09791E-05	1.60067E-05
R/G	rs190282707	-1.919	0.996	N	0.617	0.385	None	gnomAD-2.1.1	1.07135E-04	None	None	None	None	N	None	1.23987E-03	0	None	0	0	None	0	None	0	0	0
R/G	rs190282707	-1.919	0.996	N	0.617	0.385	None	gnomAD-3.1.2	2.76051E-04	None	None	None	None	N	None	9.89764E-04	6.55E-05	0	0	0	None	0	0	0	0	0
R/G	rs190282707	-1.919	0.996	N	0.617	0.385	None	gnomAD-4.0.0	4.52359E-05	None	None	None	None	N	None	9.06522E-04	3.33267E-05	None	0	0	None	0	0	0	0	4.802E-05
R/H	rs149375775	-1.782	1.0	N	0.55	0.369	None	gnomAD-2.1.1	2.78548E-04	None	None	None	None	N	None	2.52108E-03	2.2627E-04	None	0	5.13E-05	None	0	None	0	3.91E-05	4.21585E-04
R/H	rs149375775	-1.782	1.0	N	0.55	0.369	None	gnomAD-3.1.2	8.74011E-04	None	None	None	None	N	None	3.01612E-03	1.30959E-04	0	0	0	None	0	0	4.41E-05	0	1.43541E-03
R/H	rs149375775	-1.782	1.0	N	0.55	0.369	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	2.3E-03	0	None	None	0	0	None	None	None	0	None
R/H	rs149375775	-1.782	1.0	N	0.55	0.369	None	gnomAD-4.0.0	1.71026E-04	None	None	None	None	N	None	2.93216E-03	1.83291E-04	None	0	2.22866E-05	None	0	1.65071E-04	2.37341E-05	1.09794E-05	2.24086E-04
R/S	None	-1.715	0.992	N	0.573	0.401	None	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	4.69E-05	0
R/S	None	-1.715	0.992	N	0.573	0.401	None	gnomAD-3.1.2	8.54E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47011E-04	0	4.78469E-04
R/S	None	-1.715	0.992	N	0.573	0.401	None	gnomAD-4.0.0	4.27603E-05	None	None	None	None	N	None	5.34117E-05	0	None	0	0	None	0	0	5.25537E-05	0	4.80369E-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
R/A	0.3229	likely_benign	0.3775	ambiguous	-0.985	Destabilizing	0.985	D	0.533	neutral	None	None	None	None	N
R/C	0.1257	likely_benign	0.1373	benign	-0.944	Destabilizing	1.0	D	0.772	deleterious	N	0.472037223	None	None	N
R/D	0.7239	likely_pathogenic	0.7735	pathogenic	-0.079	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
R/E	0.3529	ambiguous	0.4216	ambiguous	0.099	Stabilizing	0.985	D	0.428	neutral	None	None	None	None	N
R/F	0.4348	ambiguous	0.5124	ambiguous	-0.471	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
R/G	0.2802	likely_benign	0.3442	ambiguous	-1.349	Destabilizing	0.996	D	0.617	neutral	N	0.446293417	None	None	N
R/H	0.0882	likely_benign	0.1011	benign	-1.496	Destabilizing	1.0	D	0.55	neutral	N	0.468650201	None	None	N
R/I	0.2301	likely_benign	0.2922	benign	0.02	Stabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
R/K	0.0862	likely_benign	0.0985	benign	-0.846	Destabilizing	0.271	N	0.263	neutral	None	None	None	None	N
R/L	0.198	likely_benign	0.2417	benign	0.02	Stabilizing	0.996	D	0.617	neutral	N	0.487062604	None	None	N
R/M	0.2381	likely_benign	0.299	benign	-0.486	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
R/N	0.527	ambiguous	0.5962	pathogenic	-0.518	Destabilizing	0.998	D	0.508	neutral	None	None	None	None	N
R/P	0.9686	likely_pathogenic	0.9752	pathogenic	-0.295	Destabilizing	1.0	D	0.742	deleterious	N	0.470763355	None	None	N
R/Q	0.0871	likely_benign	0.0914	benign	-0.529	Destabilizing	0.996	D	0.519	neutral	None	None	None	None	N
R/S	0.3396	likely_benign	0.3953	ambiguous	-1.328	Destabilizing	0.992	D	0.573	neutral	N	0.386700821	None	None	N
R/T	0.1693	likely_benign	0.2026	benign	-0.942	Destabilizing	0.993	D	0.599	neutral	None	None	None	None	N
R/V	0.2725	likely_benign	0.3252	benign	-0.295	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
R/W	0.2029	likely_benign	0.2324	benign	-0.051	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
R/Y	0.3289	likely_benign	0.3816	ambiguous	0.176	Stabilizing	0.999	D	0.757	deleterious	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.