TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25118	75577;75578;75579	chr2:178570780;178570779;178570778	chr2:179435507;179435506;179435505
N2AB	23477	70654;70655;70656	chr2:178570780;178570779;178570778	chr2:179435507;179435506;179435505
N2A	22550	67873;67874;67875	chr2:178570780;178570779;178570778	chr2:179435507;179435506;179435505
N2B	16053	48382;48383;48384	chr2:178570780;178570779;178570778	chr2:179435507;179435506;179435505
Novex-1	16178	48757;48758;48759	chr2:178570780;178570779;178570778	chr2:179435507;179435506;179435505
Novex-2	16245	48958;48959;48960	chr2:178570780;178570779;178570778	chr2:179435507;179435506;179435505
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: Ig-134
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.7559
• 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/E	rs1160362939	0.21	0.062	N	0.566	0.086	0.29527378943	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs1160362939	0.21	0.062	N	0.566	0.086	0.29527378943	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	0
K/N	rs780754941	-0.002	0.117	N	0.541	0.052	0.176091768786	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63399E-04	None	0	0	1.65673E-04
K/N	rs780754941	-0.002	0.117	N	0.541	0.052	0.176091768786	gnomAD-4.0.0	1.36859E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73491E-04	0	2.08691E-04	1.65689E-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	0.3719	ambiguous	0.3728	ambiguous	0.057	Stabilizing	0.035	N	0.553	neutral	None	None	None	None	N
K/C	0.708	likely_pathogenic	0.7105	pathogenic	-0.286	Destabilizing	0.935	D	0.578	neutral	None	None	None	None	N
K/D	0.6957	likely_pathogenic	0.6971	pathogenic	-0.103	Destabilizing	0.149	N	0.561	neutral	None	None	None	None	N
K/E	0.2173	likely_benign	0.2212	benign	-0.099	Destabilizing	0.062	N	0.566	neutral	N	0.506734161	None	None	N
K/F	0.815	likely_pathogenic	0.8246	pathogenic	-0.169	Destabilizing	0.555	D	0.583	neutral	None	None	None	None	N
K/G	0.4351	ambiguous	0.4354	ambiguous	-0.126	Destabilizing	0.149	N	0.552	neutral	None	None	None	None	N
K/H	0.3654	ambiguous	0.3596	ambiguous	-0.307	Destabilizing	0.555	D	0.584	neutral	None	None	None	None	N
K/I	0.4265	ambiguous	0.4299	ambiguous	0.458	Stabilizing	0.484	N	0.582	neutral	N	0.508121027	None	None	N
K/L	0.4133	ambiguous	0.4187	ambiguous	0.458	Stabilizing	0.149	N	0.553	neutral	None	None	None	None	N
K/M	0.2793	likely_benign	0.2848	benign	0.136	Stabilizing	0.791	D	0.576	neutral	None	None	None	None	N
K/N	0.5558	ambiguous	0.5531	ambiguous	0.117	Stabilizing	0.117	N	0.541	neutral	N	0.511006617	None	None	N
K/P	0.8206	likely_pathogenic	0.8236	pathogenic	0.351	Stabilizing	0.555	D	0.583	neutral	None	None	None	None	N
K/Q	0.1466	likely_benign	0.1404	benign	-0.031	Destabilizing	0.117	N	0.569	neutral	N	0.507254236	None	None	N
K/R	0.0724	likely_benign	0.0716	benign	-0.056	Destabilizing	None	N	0.246	neutral	N	0.440413168	None	None	N
K/S	0.4575	ambiguous	0.4543	ambiguous	-0.304	Destabilizing	0.003	N	0.242	neutral	None	None	None	None	N
K/T	0.2059	likely_benign	0.2068	benign	-0.16	Destabilizing	0.062	N	0.554	neutral	N	0.499616187	None	None	N
K/V	0.3958	ambiguous	0.4009	ambiguous	0.351	Stabilizing	0.38	N	0.571	neutral	None	None	None	None	N
K/W	0.7195	likely_pathogenic	0.7335	pathogenic	-0.228	Destabilizing	0.935	D	0.635	neutral	None	None	None	None	N
K/Y	0.6802	likely_pathogenic	0.6885	pathogenic	0.127	Stabilizing	0.555	D	0.592	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.