TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27683	83272;83273;83274	chr2:178563085;178563084;178563083	chr2:179427812;179427811;179427810
N2AB	26042	78349;78350;78351	chr2:178563085;178563084;178563083	chr2:179427812;179427811;179427810
N2A	25115	75568;75569;75570	chr2:178563085;178563084;178563083	chr2:179427812;179427811;179427810
N2B	18618	56077;56078;56079	chr2:178563085;178563084;178563083	chr2:179427812;179427811;179427810
Novex-1	18743	56452;56453;56454	chr2:178563085;178563084;178563083	chr2:179427812;179427811;179427810
Novex-2	18810	56653;56654;56655	chr2:178563085;178563084;178563083	chr2:179427812;179427811;179427810
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-141
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6191
• 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	rs1198736450	0.002	0.999	N	0.553	0.394	0.520694202979	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs1198736450	0.002	0.999	N	0.553	0.394	0.520694202979	gnomAD-4.0.0	1.59135E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.9398	likely_pathogenic	0.9268	pathogenic	0.042	Stabilizing	0.999	D	0.642	neutral	None	None	None	None	I
K/C	0.978	likely_pathogenic	0.9754	pathogenic	-0.158	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
K/D	0.9508	likely_pathogenic	0.9401	pathogenic	0.059	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
K/E	0.8555	likely_pathogenic	0.8085	pathogenic	0.069	Stabilizing	0.999	D	0.617	neutral	D	0.525133494	None	None	I
K/F	0.9967	likely_pathogenic	0.996	pathogenic	-0.144	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
K/G	0.9198	likely_pathogenic	0.9062	pathogenic	-0.163	Destabilizing	1.0	D	0.574	neutral	None	None	None	None	I
K/H	0.7792	likely_pathogenic	0.7499	pathogenic	-0.43	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
K/I	0.9809	likely_pathogenic	0.975	pathogenic	0.502	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	I
K/L	0.9431	likely_pathogenic	0.9312	pathogenic	0.502	Stabilizing	1.0	D	0.574	neutral	None	None	None	None	I
K/M	0.9127	likely_pathogenic	0.8849	pathogenic	0.247	Stabilizing	1.0	D	0.623	neutral	N	0.515565553	None	None	I
K/N	0.9084	likely_pathogenic	0.8863	pathogenic	0.219	Stabilizing	1.0	D	0.671	neutral	N	0.492648678	None	None	I
K/P	0.9829	likely_pathogenic	0.9838	pathogenic	0.377	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I
K/Q	0.5652	likely_pathogenic	0.5008	ambiguous	0.07	Stabilizing	1.0	D	0.655	neutral	N	0.517860805	None	None	I
K/R	0.1296	likely_benign	0.1216	benign	-0.068	Destabilizing	0.999	D	0.553	neutral	N	0.480342567	None	None	I
K/S	0.9362	likely_pathogenic	0.9218	pathogenic	-0.243	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
K/T	0.8463	likely_pathogenic	0.8148	pathogenic	-0.085	Destabilizing	1.0	D	0.642	neutral	N	0.497826465	None	None	I
K/V	0.9651	likely_pathogenic	0.9558	pathogenic	0.377	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	I
K/W	0.9912	likely_pathogenic	0.9895	pathogenic	-0.182	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
K/Y	0.9808	likely_pathogenic	0.9771	pathogenic	0.17	Stabilizing	1.0	D	0.607	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.