TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25518	76777;76778;76779	chr2:178569580;178569579;178569578	chr2:179434307;179434306;179434305
N2AB	23877	71854;71855;71856	chr2:178569580;178569579;178569578	chr2:179434307;179434306;179434305
N2A	22950	69073;69074;69075	chr2:178569580;178569579;178569578	chr2:179434307;179434306;179434305
N2B	16453	49582;49583;49584	chr2:178569580;178569579;178569578	chr2:179434307;179434306;179434305
Novex-1	16578	49957;49958;49959	chr2:178569580;178569579;178569578	chr2:179434307;179434306;179434305
Novex-2	16645	50158;50159;50160	chr2:178569580;178569579;178569578	chr2:179434307;179434306;179434305
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-135
• Domain position: 5
• Structural Position: 9
• Q(SASA): 0.7252
• 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/R	None	None	0.892	N	0.618	0.295	0.275641507738	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9154	likely_pathogenic	0.9204	pathogenic	-0.037	Destabilizing	0.845	D	0.585	neutral	None	None	None	None	I
K/C	0.9621	likely_pathogenic	0.9626	pathogenic	-0.3	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
K/D	0.9011	likely_pathogenic	0.9082	pathogenic	0.142	Stabilizing	0.975	D	0.605	neutral	None	None	None	None	I
K/E	0.7146	likely_pathogenic	0.7416	pathogenic	0.183	Stabilizing	0.892	D	0.638	neutral	N	0.484359202	None	None	I
K/F	0.9933	likely_pathogenic	0.9935	pathogenic	-0.1	Destabilizing	0.987	D	0.661	neutral	None	None	None	None	I
K/G	0.8568	likely_pathogenic	0.8612	pathogenic	-0.275	Destabilizing	0.975	D	0.528	neutral	None	None	None	None	I
K/H	0.6703	likely_pathogenic	0.685	pathogenic	-0.471	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
K/I	0.9688	likely_pathogenic	0.9698	pathogenic	0.522	Stabilizing	0.967	D	0.651	neutral	N	0.506048309	None	None	I
K/L	0.9216	likely_pathogenic	0.9262	pathogenic	0.522	Stabilizing	0.845	D	0.532	neutral	None	None	None	None	I
K/M	0.8672	likely_pathogenic	0.8722	pathogenic	0.137	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	I
K/N	0.8134	likely_pathogenic	0.8212	pathogenic	0.066	Stabilizing	0.967	D	0.641	neutral	N	0.485880139	None	None	I
K/P	0.9705	likely_pathogenic	0.9751	pathogenic	0.365	Stabilizing	0.987	D	0.638	neutral	None	None	None	None	I
K/Q	0.4048	ambiguous	0.4169	ambiguous	-0.016	Destabilizing	0.983	D	0.665	neutral	D	0.522530332	None	None	I
K/R	0.1106	likely_benign	0.1122	benign	-0.126	Destabilizing	0.892	D	0.618	neutral	N	0.510158468	None	None	I
K/S	0.8857	likely_pathogenic	0.8929	pathogenic	-0.424	Destabilizing	0.845	D	0.625	neutral	None	None	None	None	I
K/T	0.7681	likely_pathogenic	0.7857	pathogenic	-0.219	Destabilizing	0.025	N	0.379	neutral	N	0.500768391	None	None	I
K/V	0.9434	likely_pathogenic	0.9457	pathogenic	0.365	Stabilizing	0.95	D	0.523	neutral	None	None	None	None	I
K/W	0.9799	likely_pathogenic	0.9819	pathogenic	-0.128	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
K/Y	0.9579	likely_pathogenic	0.9613	pathogenic	0.209	Stabilizing	0.996	D	0.619	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.