TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25398	76417;76418;76419	chr2:178569940;178569939;178569938	chr2:179434667;179434666;179434665
N2AB	23757	71494;71495;71496	chr2:178569940;178569939;178569938	chr2:179434667;179434666;179434665
N2A	22830	68713;68714;68715	chr2:178569940;178569939;178569938	chr2:179434667;179434666;179434665
N2B	16333	49222;49223;49224	chr2:178569940;178569939;178569938	chr2:179434667;179434666;179434665
Novex-1	16458	49597;49598;49599	chr2:178569940;178569939;178569938	chr2:179434667;179434666;179434665
Novex-2	16525	49798;49799;49800	chr2:178569940;178569939;178569938	chr2:179434667;179434666;179434665
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: Fn3-72
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3412
• 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/M	None	None	0.997	N	0.685	0.293	0.284539287134	gnomAD-4.0.0	1.5933E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86175E-06	0	0
K/R	rs1467808986	0.198	0.027	N	0.359	0.066	0.218845423259	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
K/R	rs1467808986	0.198	0.027	N	0.359	0.066	0.218845423259	gnomAD-4.0.0	1.5933E-06	None	None	None	None	N	None	0	0	None	0	2.78025E-05	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	0.5021	ambiguous	0.5172	ambiguous	-0.452	Destabilizing	0.717	D	0.56	neutral	None	None	None	None	N
K/C	0.7297	likely_pathogenic	0.7662	pathogenic	-0.379	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
K/D	0.8896	likely_pathogenic	0.8954	pathogenic	-0.412	Destabilizing	0.947	D	0.581	neutral	None	None	None	None	N
K/E	0.3679	ambiguous	0.3603	ambiguous	-0.329	Destabilizing	0.792	D	0.519	neutral	N	0.501583765	None	None	N
K/F	0.8245	likely_pathogenic	0.8259	pathogenic	-0.254	Destabilizing	0.973	D	0.809	deleterious	None	None	None	None	N
K/G	0.7441	likely_pathogenic	0.7768	pathogenic	-0.805	Destabilizing	0.835	D	0.592	neutral	None	None	None	None	N
K/H	0.3671	ambiguous	0.3736	ambiguous	-1.266	Destabilizing	0.998	D	0.69	prob.delet.	None	None	None	None	N
K/I	0.403	ambiguous	0.3934	ambiguous	0.452	Stabilizing	0.947	D	0.809	deleterious	None	None	None	None	N
K/L	0.4558	ambiguous	0.4353	ambiguous	0.452	Stabilizing	0.717	D	0.607	neutral	None	None	None	None	N
K/M	0.2916	likely_benign	0.28	benign	0.486	Stabilizing	0.997	D	0.685	prob.delet.	N	0.516398502	None	None	N
K/N	0.684	likely_pathogenic	0.6929	pathogenic	-0.443	Destabilizing	0.931	D	0.554	neutral	N	0.484238665	None	None	N
K/P	0.7941	likely_pathogenic	0.7975	pathogenic	0.181	Stabilizing	0.973	D	0.683	prob.neutral	None	None	None	None	N
K/Q	0.1837	likely_benign	0.1828	benign	-0.568	Destabilizing	0.931	D	0.591	neutral	N	0.511550042	None	None	N
K/R	0.0823	likely_benign	0.0858	benign	-0.64	Destabilizing	0.027	N	0.359	neutral	N	0.48417144	None	None	N
K/S	0.6804	likely_pathogenic	0.7013	pathogenic	-1.0	Destabilizing	0.717	D	0.469	neutral	None	None	None	None	N
K/T	0.2677	likely_benign	0.2765	benign	-0.724	Destabilizing	0.027	N	0.467	neutral	N	0.449335643	None	None	N
K/V	0.3742	ambiguous	0.3661	ambiguous	0.181	Stabilizing	0.899	D	0.545	neutral	None	None	None	None	N
K/W	0.8156	likely_pathogenic	0.8302	pathogenic	-0.176	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
K/Y	0.7123	likely_pathogenic	0.7168	pathogenic	0.129	Stabilizing	0.991	D	0.831	deleterious	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.