TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14372	43339;43340;43341	chr2:178633017;178633016;178633015	chr2:179497744;179497743;179497742
N2AB	12731	38416;38417;38418	chr2:178633017;178633016;178633015	chr2:179497744;179497743;179497742
N2A	11804	35635;35636;35637	chr2:178633017;178633016;178633015	chr2:179497744;179497743;179497742
N2B	5307	16144;16145;16146	chr2:178633017;178633016;178633015	chr2:179497744;179497743;179497742
Novex-1	5432	16519;16520;16521	chr2:178633017;178633016;178633015	chr2:179497744;179497743;179497742
Novex-2	5499	16720;16721;16722	chr2:178633017;178633016;178633015	chr2:179497744;179497743;179497742
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-94
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.1721
• 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	rs1240174591	-1.052	0.999	N	0.669	0.287	0.201204373187	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
K/Q	rs1240174591	-1.052	0.999	N	0.669	0.287	0.201204373187	gnomAD-4.0.0	2.73814E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59912E-06	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	0.7868	likely_pathogenic	0.7842	pathogenic	-0.591	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
K/C	0.8841	likely_pathogenic	0.8719	pathogenic	-0.581	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
K/D	0.9084	likely_pathogenic	0.8974	pathogenic	-0.63	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
K/E	0.4608	ambiguous	0.4761	ambiguous	-0.499	Destabilizing	0.997	D	0.752	deleterious	N	0.499091072	None	None	N
K/F	0.9354	likely_pathogenic	0.9362	pathogenic	-0.107	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
K/G	0.8634	likely_pathogenic	0.8531	pathogenic	-0.999	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
K/H	0.5242	ambiguous	0.4951	ambiguous	-1.416	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/I	0.5398	ambiguous	0.5822	pathogenic	0.486	Stabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
K/L	0.6527	likely_pathogenic	0.6685	pathogenic	0.486	Stabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
K/M	0.4204	ambiguous	0.4528	ambiguous	0.414	Stabilizing	1.0	D	0.809	deleterious	N	0.448638733	None	None	N
K/N	0.6573	likely_pathogenic	0.6555	pathogenic	-0.793	Destabilizing	0.999	D	0.705	prob.delet.	N	0.499933543	None	None	N
K/P	0.9883	likely_pathogenic	0.9873	pathogenic	0.157	Stabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
K/Q	0.2732	likely_benign	0.2701	benign	-0.803	Destabilizing	0.999	D	0.669	prob.neutral	N	0.486604073	None	None	N
K/R	0.1102	likely_benign	0.1113	benign	-0.951	Destabilizing	0.997	D	0.666	prob.neutral	N	0.434838305	None	None	N
K/S	0.7651	likely_pathogenic	0.753	pathogenic	-1.335	Destabilizing	0.998	D	0.725	deleterious	None	None	None	None	N
K/T	0.3184	likely_benign	0.3455	ambiguous	-0.996	Destabilizing	0.999	D	0.785	deleterious	N	0.412070513	None	None	N
K/V	0.5746	likely_pathogenic	0.5975	pathogenic	0.157	Stabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
K/W	0.9087	likely_pathogenic	0.9093	pathogenic	-0.049	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
K/Y	0.8223	likely_pathogenic	0.8191	pathogenic	0.234	Stabilizing	1.0	D	0.887	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.