TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22481	67666;67667;67668	chr2:178579756;178579755;178579754	chr2:179444483;179444482;179444481
N2AB	20840	62743;62744;62745	chr2:178579756;178579755;178579754	chr2:179444483;179444482;179444481
N2A	19913	59962;59963;59964	chr2:178579756;178579755;178579754	chr2:179444483;179444482;179444481
N2B	13416	40471;40472;40473	chr2:178579756;178579755;178579754	chr2:179444483;179444482;179444481
Novex-1	13541	40846;40847;40848	chr2:178579756;178579755;178579754	chr2:179444483;179444482;179444481
Novex-2	13608	41047;41048;41049	chr2:178579756;178579755;178579754	chr2:179444483;179444482;179444481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-51
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2181
• 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
S/R	rs1268356218	-0.381	1.0	N	0.811	0.61	0.358340041657	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/R	rs1268356218	-0.381	1.0	N	0.811	0.61	0.358340041657	gnomAD-4.0.0	1.59227E-06	None	None	None	None	I	None	0	2.28728E-05	None	0	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
S/A	0.242	likely_benign	0.2042	benign	-0.465	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	I
S/C	0.2223	likely_benign	0.177	benign	-0.31	Destabilizing	1.0	D	0.797	deleterious	N	0.475006543	None	None	I
S/D	0.9067	likely_pathogenic	0.8791	pathogenic	-0.64	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
S/E	0.9304	likely_pathogenic	0.9104	pathogenic	-0.708	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
S/F	0.7704	likely_pathogenic	0.6847	pathogenic	-0.954	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
S/G	0.2987	likely_benign	0.2472	benign	-0.625	Destabilizing	0.999	D	0.587	neutral	N	0.463412158	None	None	I
S/H	0.7962	likely_pathogenic	0.7256	pathogenic	-1.203	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
S/I	0.8067	likely_pathogenic	0.7257	pathogenic	-0.163	Destabilizing	1.0	D	0.815	deleterious	N	0.507478844	None	None	I
S/K	0.9665	likely_pathogenic	0.951	pathogenic	-0.669	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
S/L	0.4655	ambiguous	0.3689	ambiguous	-0.163	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
S/M	0.6596	likely_pathogenic	0.5491	ambiguous	0.322	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
S/N	0.5438	ambiguous	0.4931	ambiguous	-0.508	Destabilizing	0.999	D	0.705	prob.neutral	N	0.496122538	None	None	I
S/P	0.9895	likely_pathogenic	0.9847	pathogenic	-0.234	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
S/Q	0.8672	likely_pathogenic	0.8186	pathogenic	-0.845	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
S/R	0.9473	likely_pathogenic	0.9267	pathogenic	-0.375	Destabilizing	1.0	D	0.811	deleterious	N	0.48882793	None	None	I
S/T	0.2364	likely_benign	0.1884	benign	-0.519	Destabilizing	0.999	D	0.603	neutral	N	0.475296032	None	None	I
S/V	0.7134	likely_pathogenic	0.6007	pathogenic	-0.234	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
S/W	0.8443	likely_pathogenic	0.7917	pathogenic	-0.938	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
S/Y	0.7108	likely_pathogenic	0.6381	pathogenic	-0.664	Destabilizing	1.0	D	0.831	deleterious	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.