TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29479	88660;88661;88662	chr2:178555024;178555023;178555022	chr2:179419751;179419750;179419749
N2AB	27838	83737;83738;83739	chr2:178555024;178555023;178555022	chr2:179419751;179419750;179419749
N2A	26911	80956;80957;80958	chr2:178555024;178555023;178555022	chr2:179419751;179419750;179419749
N2B	20414	61465;61466;61467	chr2:178555024;178555023;178555022	chr2:179419751;179419750;179419749
Novex-1	20539	61840;61841;61842	chr2:178555024;178555023;178555022	chr2:179419751;179419750;179419749
Novex-2	20606	62041;62042;62043	chr2:178555024;178555023;178555022	chr2:179419751;179419750;179419749
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-146
• Domain position: 36
• Structural Position: 55
• Q(SASA): 0.6124
• 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/Q	rs1700830779	None	0.968	N	0.413	0.25	0.339316883193	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs1700830779	None	0.968	N	0.413	0.25	0.339316883193	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	2.41255E-05	0	None	0	0	None	0	0	0	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	0.2971	likely_benign	0.2578	benign	0.036	Stabilizing	0.919	D	0.45	neutral	None	None	None	None	N
K/C	0.5344	ambiguous	0.5087	ambiguous	-0.178	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
K/D	0.5136	ambiguous	0.4506	ambiguous	None	Stabilizing	0.851	D	0.423	neutral	None	None	None	None	N
K/E	0.1315	likely_benign	0.1142	benign	0.023	Stabilizing	0.896	D	0.448	neutral	N	0.511566764	None	None	N
K/F	0.716	likely_pathogenic	0.6662	pathogenic	-0.073	Destabilizing	0.988	D	0.499	neutral	None	None	None	None	N
K/G	0.4489	ambiguous	0.3818	ambiguous	-0.189	Destabilizing	0.851	D	0.445	neutral	None	None	None	None	N
K/H	0.2797	likely_benign	0.2625	benign	-0.442	Destabilizing	0.076	N	0.385	neutral	None	None	None	None	N
K/I	0.2492	likely_benign	0.2185	benign	0.558	Stabilizing	0.984	D	0.496	neutral	N	0.4885833	None	None	N
K/L	0.3172	likely_benign	0.283	benign	0.558	Stabilizing	0.919	D	0.423	neutral	None	None	None	None	N
K/M	0.1775	likely_benign	0.1623	benign	0.229	Stabilizing	0.999	D	0.451	neutral	None	None	None	None	N
K/N	0.3651	ambiguous	0.3232	benign	0.161	Stabilizing	0.026	N	0.246	neutral	N	0.487822831	None	None	N
K/P	0.9538	likely_pathogenic	0.9277	pathogenic	0.413	Stabilizing	0.996	D	0.434	neutral	None	None	None	None	N
K/Q	0.1057	likely_benign	0.1021	benign	0.034	Stabilizing	0.968	D	0.413	neutral	N	0.506544946	None	None	N
K/R	0.078	likely_benign	0.0775	benign	-0.108	Destabilizing	0.026	N	0.24	neutral	N	0.520399678	None	None	N
K/S	0.3729	ambiguous	0.3294	benign	-0.284	Destabilizing	0.851	D	0.417	neutral	None	None	None	None	N
K/T	0.1399	likely_benign	0.1256	benign	-0.108	Destabilizing	0.896	D	0.428	neutral	D	0.53619585	None	None	N
K/V	0.2116	likely_benign	0.1902	benign	0.413	Stabilizing	0.988	D	0.445	neutral	None	None	None	None	N
K/W	0.729	likely_pathogenic	0.6857	pathogenic	-0.111	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
K/Y	0.5798	likely_pathogenic	0.5317	ambiguous	0.23	Stabilizing	0.976	D	0.48	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.