TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31654	95185;95186;95187	chr2:178546371;178546370;178546369	chr2:179411098;179411097;179411096
N2AB	30013	90262;90263;90264	chr2:178546371;178546370;178546369	chr2:179411098;179411097;179411096
N2A	29086	87481;87482;87483	chr2:178546371;178546370;178546369	chr2:179411098;179411097;179411096
N2B	22589	67990;67991;67992	chr2:178546371;178546370;178546369	chr2:179411098;179411097;179411096
Novex-1	22714	68365;68366;68367	chr2:178546371;178546370;178546369	chr2:179411098;179411097;179411096
Novex-2	22781	68566;68567;68568	chr2:178546371;178546370;178546369	chr2:179411098;179411097;179411096
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-152
• Domain position: 34
• Structural Position: 55
• Q(SASA): 0.5149
• 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	None	None	0.896	N	0.461	0.236	0.375861065471	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	2.28655E-05	None	0	0	None	0	0	0	0	0
K/N	None	None	0.968	N	0.386	0.294	0.298056030225	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.2417	likely_benign	0.2467	benign	-0.006	Destabilizing	0.919	D	0.477	neutral	None	None	None	None	N
K/C	0.5289	ambiguous	0.5549	ambiguous	-0.025	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
K/D	0.448	ambiguous	0.4554	ambiguous	0.177	Stabilizing	0.988	D	0.414	neutral	None	None	None	None	N
K/E	0.1283	likely_benign	0.1319	benign	0.199	Stabilizing	0.896	D	0.461	neutral	N	0.472509731	None	None	N
K/F	0.6918	likely_pathogenic	0.7164	pathogenic	-0.111	Destabilizing	0.996	D	0.592	neutral	None	None	None	None	N
K/G	0.3573	ambiguous	0.3638	ambiguous	-0.252	Destabilizing	0.959	D	0.441	neutral	None	None	None	None	N
K/H	0.2288	likely_benign	0.247	benign	-0.638	Destabilizing	0.997	D	0.485	neutral	None	None	None	None	N
K/I	0.2786	likely_benign	0.2861	benign	0.572	Stabilizing	0.976	D	0.594	neutral	None	None	None	None	N
K/L	0.3018	likely_benign	0.3143	benign	0.572	Stabilizing	0.919	D	0.453	neutral	None	None	None	None	N
K/M	0.1881	likely_benign	0.1896	benign	0.45	Stabilizing	0.999	D	0.486	neutral	D	0.536697282	None	None	N
K/N	0.3414	ambiguous	0.3478	ambiguous	0.332	Stabilizing	0.968	D	0.386	neutral	N	0.507547811	None	None	N
K/P	0.921	likely_pathogenic	0.9239	pathogenic	0.409	Stabilizing	0.996	D	0.464	neutral	None	None	None	None	N
K/Q	0.0983	likely_benign	0.1032	benign	0.151	Stabilizing	0.968	D	0.427	neutral	N	0.469642784	None	None	N
K/R	0.0687	likely_benign	0.0712	benign	-0.046	Destabilizing	0.026	N	0.273	neutral	N	0.474069956	None	None	N
K/S	0.3022	likely_benign	0.3192	benign	-0.202	Destabilizing	0.851	D	0.431	neutral	None	None	None	None	N
K/T	0.1238	likely_benign	0.1251	benign	-0.017	Destabilizing	0.211	N	0.307	neutral	D	0.524882778	None	None	N
K/V	0.2194	likely_benign	0.226	benign	0.409	Stabilizing	0.976	D	0.433	neutral	None	None	None	None	N
K/W	0.6466	likely_pathogenic	0.6761	pathogenic	-0.088	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
K/Y	0.5565	ambiguous	0.5681	pathogenic	0.258	Stabilizing	0.996	D	0.551	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.