TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8638	26137;26138;26139	chr2:178715502;178715501;178715500	chr2:179580229;179580228;179580227
N2AB	8321	25186;25187;25188	chr2:178715502;178715501;178715500	chr2:179580229;179580228;179580227
N2A	7394	22405;22406;22407	chr2:178715502;178715501;178715500	chr2:179580229;179580228;179580227
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-71
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.4504
• 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/N	None	None	0.447	N	0.275	0.059	0.197625483188	gnomAD-4.0.0	1.59765E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87396E-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	0.3962	ambiguous	0.2985	benign	-0.53	Destabilizing	0.181	N	0.412	neutral	None	None	None	None	N
K/C	0.7289	likely_pathogenic	0.65	pathogenic	-0.662	Destabilizing	0.989	D	0.447	neutral	None	None	None	None	N
K/D	0.6631	likely_pathogenic	0.5635	ambiguous	0.297	Stabilizing	0.517	D	0.393	neutral	None	None	None	None	N
K/E	0.2136	likely_benign	0.1632	benign	0.389	Stabilizing	0.091	N	0.286	neutral	N	0.49080749	None	None	N
K/F	0.7201	likely_pathogenic	0.629	pathogenic	-0.388	Destabilizing	0.599	D	0.489	neutral	None	None	None	None	N
K/G	0.6929	likely_pathogenic	0.568	pathogenic	-0.854	Destabilizing	0.517	D	0.437	neutral	None	None	None	None	N
K/H	0.2779	likely_benign	0.2401	benign	-1.15	Destabilizing	0.759	D	0.435	neutral	None	None	None	None	N
K/I	0.2265	likely_benign	0.1911	benign	0.289	Stabilizing	None	N	0.421	neutral	N	0.451694528	None	None	N
K/L	0.2963	likely_benign	0.2372	benign	0.289	Stabilizing	0.006	N	0.433	neutral	None	None	None	None	N
K/M	0.181	likely_benign	0.1508	benign	0.152	Stabilizing	0.31	N	0.439	neutral	None	None	None	None	N
K/N	0.4627	ambiguous	0.381	ambiguous	-0.201	Destabilizing	0.447	N	0.275	neutral	N	0.499024328	None	None	N
K/P	0.9399	likely_pathogenic	0.8763	pathogenic	0.046	Stabilizing	0.884	D	0.449	neutral	None	None	None	None	N
K/Q	0.1338	likely_benign	0.1176	benign	-0.324	Destabilizing	0.089	N	0.392	neutral	N	0.487940543	None	None	N
K/R	0.0925	likely_benign	0.0829	benign	-0.359	Destabilizing	None	N	0.214	neutral	N	0.465970547	None	None	N
K/S	0.4684	ambiguous	0.3766	ambiguous	-0.964	Destabilizing	0.017	N	0.075	neutral	None	None	None	None	N
K/T	0.1378	likely_benign	0.1114	benign	-0.667	Destabilizing	0.001	N	0.155	neutral	N	0.407690248	None	None	N
K/V	0.2353	likely_benign	0.1954	benign	0.046	Stabilizing	0.003	N	0.42	neutral	None	None	None	None	N
K/W	0.7341	likely_pathogenic	0.6545	pathogenic	-0.218	Destabilizing	0.992	D	0.511	neutral	None	None	None	None	N
K/Y	0.6049	likely_pathogenic	0.519	ambiguous	0.095	Stabilizing	0.519	D	0.451	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.