TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24036	72331;72332;72333	chr2:178574026;178574025;178574024	chr2:179438753;179438752;179438751
N2AB	22395	67408;67409;67410	chr2:178574026;178574025;178574024	chr2:179438753;179438752;179438751
N2A	21468	64627;64628;64629	chr2:178574026;178574025;178574024	chr2:179438753;179438752;179438751
N2B	14971	45136;45137;45138	chr2:178574026;178574025;178574024	chr2:179438753;179438752;179438751
Novex-1	15096	45511;45512;45513	chr2:178574026;178574025;178574024	chr2:179438753;179438752;179438751
Novex-2	15163	45712;45713;45714	chr2:178574026;178574025;178574024	chr2:179438753;179438752;179438751
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-131
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.641
• 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	rs544263357	-0.134	0.704	N	0.513	0.284	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	1.29316E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs544263357	-0.134	0.704	N	0.513	0.284	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs544263357	-0.134	0.704	N	0.513	0.284	None	gnomAD-4.0.0	2.47933E-06	None	None	None	None	I	None	4.00555E-05	1.6675E-05	None	0	0	None	0	0	0	0	0
K/Q	None	-0.054	0.31	D	0.257	0.242	0.245660935333	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	6.47E-05	5.8E-05	None	0	0	None	0	None	0	0	0
K/Q	None	-0.054	0.31	D	0.257	0.242	0.245660935333	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	None	-0.054	0.31	D	0.257	0.242	0.245660935333	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
K/Q	None	-0.054	0.31	D	0.257	0.242	0.245660935333	gnomAD-4.0.0	5.5781E-06	None	None	None	None	I	None	1.33301E-05	5.00083E-05	None	0	0	None	0	0	4.23869E-06	0	0
K/R	rs1709185924	None	0.92	N	0.465	0.153	0.391313282164	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.3493	ambiguous	0.3669	ambiguous	0.034	Stabilizing	0.759	D	0.426	neutral	None	None	None	None	I
K/C	0.7387	likely_pathogenic	0.7544	pathogenic	-0.303	Destabilizing	0.999	D	0.427	neutral	None	None	None	None	I
K/D	0.6532	likely_pathogenic	0.6677	pathogenic	-0.17	Destabilizing	0.939	D	0.405	neutral	None	None	None	None	I
K/E	0.1908	likely_benign	0.2142	benign	-0.185	Destabilizing	0.704	D	0.513	neutral	N	0.495383803	None	None	I
K/F	0.8185	likely_pathogenic	0.8324	pathogenic	-0.303	Destabilizing	0.997	D	0.427	neutral	None	None	None	None	I
K/G	0.4436	ambiguous	0.4574	ambiguous	-0.103	Destabilizing	0.939	D	0.427	neutral	None	None	None	None	I
K/H	0.3474	ambiguous	0.3583	ambiguous	-0.277	Destabilizing	0.991	D	0.402	neutral	None	None	None	None	I
K/I	0.408	ambiguous	0.4401	ambiguous	0.312	Stabilizing	0.991	D	0.433	neutral	None	None	None	None	I
K/L	0.3964	ambiguous	0.4258	ambiguous	0.312	Stabilizing	0.969	D	0.427	neutral	None	None	None	None	I
K/M	0.2678	likely_benign	0.2894	benign	0.049	Stabilizing	0.996	D	0.402	neutral	N	0.514932356	None	None	I
K/N	0.5141	ambiguous	0.5452	ambiguous	0.149	Stabilizing	0.92	D	0.425	neutral	D	0.529651093	None	None	I
K/P	0.7425	likely_pathogenic	0.7401	pathogenic	0.244	Stabilizing	0.991	D	0.385	neutral	None	None	None	None	I
K/Q	0.1305	likely_benign	0.1412	benign	-0.017	Destabilizing	0.31	N	0.257	neutral	D	0.52570671	None	None	I
K/R	0.0748	likely_benign	0.0757	benign	-0.044	Destabilizing	0.92	D	0.465	neutral	N	0.43092968	None	None	I
K/S	0.4038	ambiguous	0.43	ambiguous	-0.246	Destabilizing	0.2	N	0.24	neutral	None	None	None	None	I
K/T	0.177	likely_benign	0.1928	benign	-0.14	Destabilizing	0.852	D	0.427	neutral	D	0.533518117	None	None	I
K/V	0.387	ambiguous	0.4184	ambiguous	0.244	Stabilizing	0.969	D	0.421	neutral	None	None	None	None	I
K/W	0.7416	likely_pathogenic	0.7385	pathogenic	-0.386	Destabilizing	0.999	D	0.502	neutral	None	None	None	None	I
K/Y	0.6902	likely_pathogenic	0.6923	pathogenic	-0.025	Destabilizing	0.997	D	0.429	neutral	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.