TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9125	27598;27599;27600	chr2:178712549;178712548;178712547	chr2:179577276;179577275;179577274
N2AB	8808	26647;26648;26649	chr2:178712549;178712548;178712547	chr2:179577276;179577275;179577274
N2A	7881	23866;23867;23868	chr2:178712549;178712548;178712547	chr2:179577276;179577275;179577274
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-77
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.7931
• 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/N	rs749332790	0.196	0.984	N	0.411	0.176	0.187945064343	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	6.49E-05	0	None	0	0	None	0	None	0	0	0
K/N	rs749332790	0.196	0.984	N	0.411	0.176	0.187945064343	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs749332790	0.196	0.984	N	0.411	0.176	0.187945064343	gnomAD-4.0.0	1.31406E-05	None	None	None	None	I	None	4.82416E-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	0.2165	likely_benign	0.1954	benign	-0.211	Destabilizing	0.034	N	0.267	neutral	None	None	None	None	I
K/C	0.6894	likely_pathogenic	0.6221	pathogenic	-0.308	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	I
K/D	0.4717	ambiguous	0.4304	ambiguous	0.373	Stabilizing	0.976	D	0.423	neutral	None	None	None	None	I
K/E	0.1206	likely_benign	0.1098	benign	0.405	Stabilizing	0.811	D	0.477	neutral	N	0.370989502	None	None	I
K/F	0.6882	likely_pathogenic	0.6463	pathogenic	-0.324	Destabilizing	0.976	D	0.523	neutral	None	None	None	None	I
K/G	0.3965	ambiguous	0.3342	benign	-0.456	Destabilizing	0.851	D	0.519	neutral	None	None	None	None	I
K/H	0.3515	ambiguous	0.3188	benign	-0.796	Destabilizing	0.997	D	0.424	neutral	None	None	None	None	I
K/I	0.2171	likely_benign	0.2068	benign	0.364	Stabilizing	0.938	D	0.489	neutral	N	0.46530796	None	None	I
K/L	0.2799	likely_benign	0.2522	benign	0.364	Stabilizing	0.034	N	0.341	neutral	None	None	None	None	I
K/M	0.1484	likely_benign	0.1456	benign	0.26	Stabilizing	0.976	D	0.428	neutral	None	None	None	None	I
K/N	0.2983	likely_benign	0.2604	benign	0.157	Stabilizing	0.984	D	0.411	neutral	N	0.494630789	None	None	I
K/P	0.4748	ambiguous	0.3926	ambiguous	0.202	Stabilizing	0.988	D	0.441	neutral	None	None	None	None	I
K/Q	0.1291	likely_benign	0.1168	benign	-0.017	Destabilizing	0.437	N	0.288	neutral	N	0.466001393	None	None	I
K/R	0.0915	likely_benign	0.0841	benign	-0.124	Destabilizing	0.896	D	0.476	neutral	N	0.450205221	None	None	I
K/S	0.3241	likely_benign	0.2743	benign	-0.486	Destabilizing	0.851	D	0.463	neutral	None	None	None	None	I
K/T	0.1308	likely_benign	0.1176	benign	-0.281	Destabilizing	0.896	D	0.487	neutral	N	0.450031863	None	None	I
K/V	0.2226	likely_benign	0.2071	benign	0.202	Stabilizing	0.851	D	0.515	neutral	None	None	None	None	I
K/W	0.7465	likely_pathogenic	0.7006	pathogenic	-0.247	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
K/Y	0.5353	ambiguous	0.499	ambiguous	0.095	Stabilizing	0.996	D	0.501	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.