TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18174	54745;54746;54747	chr2:178604167;178604166;178604165	chr2:179468894;179468893;179468892
N2AB	16533	49822;49823;49824	chr2:178604167;178604166;178604165	chr2:179468894;179468893;179468892
N2A	15606	47041;47042;47043	chr2:178604167;178604166;178604165	chr2:179468894;179468893;179468892
N2B	9109	27550;27551;27552	chr2:178604167;178604166;178604165	chr2:179468894;179468893;179468892
Novex-1	9234	27925;27926;27927	chr2:178604167;178604166;178604165	chr2:179468894;179468893;179468892
Novex-2	9301	28126;28127;28128	chr2:178604167;178604166;178604165	chr2:179468894;179468893;179468892
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: Fn3-20
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4286
• 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	0.055	N	0.467	0.077	0.154104182512	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94401E-04	None	0	0	0	0	0
K/N	None	None	0.055	N	0.467	0.077	0.154104182512	gnomAD-4.0.0	1.24062E-06	None	None	None	None	N	None	0	0	None	0	2.23654E-05	None	0	0	8.48228E-07	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	0.2233	likely_benign	0.1639	benign	-0.202	Destabilizing	None	N	0.264	neutral	None	None	None	None	N
K/C	0.5193	ambiguous	0.4864	ambiguous	-0.301	Destabilizing	0.676	D	0.503	neutral	None	None	None	None	N
K/D	0.5411	ambiguous	0.4304	ambiguous	0.254	Stabilizing	0.072	N	0.561	neutral	None	None	None	None	N
K/E	0.126	likely_benign	0.0991	benign	0.323	Stabilizing	0.012	N	0.481	neutral	N	0.452219311	None	None	N
K/F	0.6465	likely_pathogenic	0.5605	ambiguous	-0.033	Destabilizing	0.214	N	0.517	neutral	None	None	None	None	N
K/G	0.4459	ambiguous	0.3302	benign	-0.509	Destabilizing	0.031	N	0.467	neutral	None	None	None	None	N
K/H	0.2535	likely_benign	0.2121	benign	-0.796	Destabilizing	0.214	N	0.541	neutral	None	None	None	None	N
K/I	0.211	likely_benign	0.1837	benign	0.56	Stabilizing	0.01	N	0.547	neutral	N	0.491239059	None	None	N
K/L	0.2773	likely_benign	0.2149	benign	0.56	Stabilizing	0.016	N	0.462	neutral	None	None	None	None	N
K/M	0.1864	likely_benign	0.1554	benign	0.291	Stabilizing	0.214	N	0.542	neutral	None	None	None	None	N
K/N	0.3818	ambiguous	0.3014	benign	0.006	Stabilizing	0.055	N	0.467	neutral	N	0.514595922	None	None	N
K/P	0.9265	likely_pathogenic	0.8664	pathogenic	0.337	Stabilizing	0.136	N	0.58	neutral	None	None	None	None	N
K/Q	0.1038	likely_benign	0.0896	benign	-0.087	Destabilizing	None	N	0.289	neutral	N	0.470380998	None	None	N
K/R	0.0745	likely_benign	0.0719	benign	-0.307	Destabilizing	None	N	0.287	neutral	N	0.446234701	None	None	N
K/S	0.3194	likely_benign	0.2333	benign	-0.6	Destabilizing	0.003	N	0.212	neutral	None	None	None	None	N
K/T	0.1085	likely_benign	0.088	benign	-0.343	Destabilizing	None	N	0.286	neutral	N	0.416546513	None	None	N
K/V	0.1524	likely_benign	0.1325	benign	0.337	Stabilizing	None	N	0.343	neutral	None	None	None	None	N
K/W	0.7357	likely_pathogenic	0.6377	pathogenic	0.042	Stabilizing	0.864	D	0.534	neutral	None	None	None	None	N
K/Y	0.5869	likely_pathogenic	0.4966	ambiguous	0.342	Stabilizing	0.356	N	0.536	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.