TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1370	4333;4334;4335	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699
N2AB	1370	4333;4334;4335	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699
N2A	1370	4333;4334;4335	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699
N2B	1324	4195;4196;4197	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699
Novex-1	1324	4195;4196;4197	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699
Novex-2	1324	4195;4196;4197	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699
Novex-3	1370	4333;4334;4335	chr2:178778974;178778973;178778972	chr2:179643701;179643700;179643699

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-5
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.9013
• 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/E	rs1453568535	0.172	0.98	N	0.465	0.335	0.379366414296	gnomAD-2.1.1	7.98E-06	None	None	None	None	I	None	0	0	None	1.98847E-04	0	None	0	None	0	0	0
K/E	rs1453568535	0.172	0.98	N	0.465	0.335	0.379366414296	gnomAD-4.0.0	3.18169E-06	None	None	None	None	I	None	0	0	None	9.5338E-05	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	0.823	likely_pathogenic	0.8124	pathogenic	-0.02	Destabilizing	0.985	D	0.491	neutral	None	None	None	None	I
K/C	0.9084	likely_pathogenic	0.901	pathogenic	-0.449	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	I
K/D	0.9617	likely_pathogenic	0.967	pathogenic	-0.268	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	I
K/E	0.7378	likely_pathogenic	0.7351	pathogenic	-0.283	Destabilizing	0.98	D	0.465	neutral	N	0.406739243	None	None	I
K/F	0.9658	likely_pathogenic	0.9646	pathogenic	-0.388	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	I
K/G	0.91	likely_pathogenic	0.9045	pathogenic	-0.14	Destabilizing	0.993	D	0.559	neutral	None	None	None	None	I
K/H	0.5868	likely_pathogenic	0.6135	pathogenic	-0.253	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	I
K/I	0.8634	likely_pathogenic	0.8555	pathogenic	0.211	Stabilizing	0.989	D	0.576	neutral	N	0.410282928	None	None	I
K/L	0.7886	likely_pathogenic	0.7943	pathogenic	0.211	Stabilizing	0.171	N	0.447	neutral	None	None	None	None	I
K/M	0.693	likely_pathogenic	0.6803	pathogenic	-0.099	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	I
K/N	0.8765	likely_pathogenic	0.8877	pathogenic	0.01	Stabilizing	0.997	D	0.456	neutral	N	0.452408785	None	None	I
K/P	0.9863	likely_pathogenic	0.9858	pathogenic	0.157	Stabilizing	0.999	D	0.545	neutral	None	None	None	None	I
K/Q	0.3774	ambiguous	0.397	ambiguous	-0.134	Destabilizing	0.994	D	0.485	neutral	N	0.363849504	None	None	I
K/R	0.1146	likely_benign	0.1194	benign	-0.1	Destabilizing	0.265	N	0.281	neutral	N	0.444774559	None	None	I
K/S	0.8759	likely_pathogenic	0.8788	pathogenic	-0.362	Destabilizing	0.971	D	0.451	neutral	None	None	None	None	I
K/T	0.7276	likely_pathogenic	0.7034	pathogenic	-0.261	Destabilizing	0.4	N	0.363	neutral	N	0.483200362	None	None	I
K/V	0.8204	likely_pathogenic	0.8042	pathogenic	0.157	Stabilizing	0.971	D	0.591	neutral	None	None	None	None	I
K/W	0.9597	likely_pathogenic	0.9579	pathogenic	-0.488	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	I
K/Y	0.9045	likely_pathogenic	0.905	pathogenic	-0.133	Destabilizing	0.999	D	0.601	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.