TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5650	17173;17174;17175	chr2:178731927;178731926;178731925	chr2:179596654;179596653;179596652
N2AB	5333	16222;16223;16224	chr2:178731927;178731926;178731925	chr2:179596654;179596653;179596652
N2A	4406	13441;13442;13443	chr2:178731927;178731926;178731925	chr2:179596654;179596653;179596652
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-40
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4448
• 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	rs1429494735	None	0.001	N	0.157	0.047	0.151104730317	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1429494735	None	0.001	N	0.157	0.047	0.151104730317	gnomAD-4.0.0	5.13398E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.59767E-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	0.4801	ambiguous	0.5145	ambiguous	-0.358	Destabilizing	0.207	N	0.326	neutral	None	None	None	None	I
K/C	0.8459	likely_pathogenic	0.8606	pathogenic	-0.514	Destabilizing	0.981	D	0.511	neutral	None	None	None	None	I
K/D	0.7291	likely_pathogenic	0.7291	pathogenic	-0.06	Destabilizing	0.388	N	0.315	neutral	None	None	None	None	I
K/E	0.221	likely_benign	0.2365	benign	0.051	Stabilizing	0.193	N	0.383	neutral	N	0.429440373	None	None	I
K/F	0.9033	likely_pathogenic	0.9182	pathogenic	-0.053	Destabilizing	0.818	D	0.443	neutral	None	None	None	None	I
K/G	0.5394	ambiguous	0.5567	ambiguous	-0.696	Destabilizing	0.002	N	0.267	neutral	None	None	None	None	I
K/H	0.4362	ambiguous	0.4661	ambiguous	-0.826	Destabilizing	0.818	D	0.293	neutral	None	None	None	None	I
K/I	0.6366	likely_pathogenic	0.6916	pathogenic	0.504	Stabilizing	0.818	D	0.445	neutral	None	None	None	None	I
K/L	0.5434	ambiguous	0.591	pathogenic	0.504	Stabilizing	0.388	N	0.399	neutral	None	None	None	None	I
K/M	0.4315	ambiguous	0.479	ambiguous	0.087	Stabilizing	0.975	D	0.289	neutral	N	0.456666392	None	None	I
K/N	0.6116	likely_pathogenic	0.6335	pathogenic	-0.406	Destabilizing	0.324	N	0.327	neutral	N	0.453045541	None	None	I
K/P	0.5644	likely_pathogenic	0.5871	pathogenic	0.247	Stabilizing	0.818	D	0.305	neutral	None	None	None	None	I
K/Q	0.1527	likely_benign	0.1659	benign	-0.391	Destabilizing	0.627	D	0.367	neutral	N	0.48324036	None	None	I
K/R	0.0805	likely_benign	0.0807	benign	-0.411	Destabilizing	0.001	N	0.157	neutral	N	0.442932532	None	None	I
K/S	0.578	likely_pathogenic	0.6121	pathogenic	-0.948	Destabilizing	0.388	N	0.334	neutral	None	None	None	None	I
K/T	0.3541	ambiguous	0.3956	ambiguous	-0.639	Destabilizing	0.324	N	0.318	neutral	N	0.487742102	None	None	I
K/V	0.5804	likely_pathogenic	0.6369	pathogenic	0.247	Stabilizing	0.69	D	0.372	neutral	None	None	None	None	I
K/W	0.8162	likely_pathogenic	0.8361	pathogenic	-0.023	Destabilizing	0.981	D	0.577	neutral	None	None	None	None	I
K/Y	0.7852	likely_pathogenic	0.8007	pathogenic	0.265	Stabilizing	0.818	D	0.411	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.