TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3104	9535;9536;9537	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645
N2AB	3104	9535;9536;9537	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645
N2A	3104	9535;9536;9537	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645
N2B	3058	9397;9398;9399	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645
Novex-1	3058	9397;9398;9399	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645
Novex-2	3058	9397;9398;9399	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645
Novex-3	3104	9535;9536;9537	chr2:178767920;178767919;178767918	chr2:179632647;179632646;179632645

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-21
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.2673
• 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/E	rs2154341451	None	0.042	N	0.313	0.269	0.29385284311	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.5694	likely_pathogenic	0.7051	pathogenic	-0.408	Destabilizing	0.055	N	0.327	neutral	None	None	None	None	N
K/C	0.8202	likely_pathogenic	0.8852	pathogenic	-0.548	Destabilizing	0.883	D	0.418	neutral	None	None	None	None	N
K/D	0.838	likely_pathogenic	0.9034	pathogenic	-0.078	Destabilizing	0.22	N	0.339	neutral	None	None	None	None	N
K/E	0.4139	ambiguous	0.5595	ambiguous	0.056	Stabilizing	0.042	N	0.313	neutral	N	0.500467494	None	None	N
K/F	0.8783	likely_pathogenic	0.9333	pathogenic	0.008	Stabilizing	0.497	N	0.445	neutral	None	None	None	None	N
K/G	0.7466	likely_pathogenic	0.8391	pathogenic	-0.789	Destabilizing	0.22	N	0.393	neutral	None	None	None	None	N
K/H	0.384	ambiguous	0.4696	ambiguous	-1.033	Destabilizing	0.667	D	0.399	neutral	None	None	None	None	N
K/I	0.4607	ambiguous	0.6173	pathogenic	0.58	Stabilizing	0.331	N	0.445	neutral	None	None	None	None	N
K/L	0.5291	ambiguous	0.6519	pathogenic	0.58	Stabilizing	0.02	N	0.34	neutral	None	None	None	None	N
K/M	0.3526	ambiguous	0.494	ambiguous	0.21	Stabilizing	0.019	N	0.252	neutral	D	0.577886743	None	None	N
K/N	0.6169	likely_pathogenic	0.7461	pathogenic	-0.503	Destabilizing	0.175	N	0.267	neutral	N	0.512062491	None	None	N
K/P	0.9566	likely_pathogenic	0.9733	pathogenic	0.281	Stabilizing	0.364	N	0.415	neutral	None	None	None	None	N
K/Q	0.1838	likely_benign	0.2407	benign	-0.454	Destabilizing	0.008	N	0.195	neutral	N	0.503046775	None	None	N
K/R	0.096	likely_benign	0.1046	benign	-0.603	Destabilizing	None	N	0.103	neutral	N	0.468360683	None	None	N
K/S	0.5949	likely_pathogenic	0.7328	pathogenic	-1.08	Destabilizing	0.011	N	0.143	neutral	None	None	None	None	N
K/T	0.2253	likely_benign	0.3503	ambiguous	-0.733	Destabilizing	0.001	N	0.19	neutral	N	0.51361781	None	None	N
K/V	0.4319	ambiguous	0.5712	pathogenic	0.281	Stabilizing	0.124	N	0.387	neutral	None	None	None	None	N
K/W	0.8602	likely_pathogenic	0.9149	pathogenic	0.057	Stabilizing	0.958	D	0.438	neutral	None	None	None	None	N
K/Y	0.7857	likely_pathogenic	0.8654	pathogenic	0.349	Stabilizing	0.667	D	0.427	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.