TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22436	67531;67532;67533	chr2:178579981;178579980;178579979	chr2:179444708;179444707;179444706
N2AB	20795	62608;62609;62610	chr2:178579981;178579980;178579979	chr2:179444708;179444707;179444706
N2A	19868	59827;59828;59829	chr2:178579981;178579980;178579979	chr2:179444708;179444707;179444706
N2B	13371	40336;40337;40338	chr2:178579981;178579980;178579979	chr2:179444708;179444707;179444706
Novex-1	13496	40711;40712;40713	chr2:178579981;178579980;178579979	chr2:179444708;179444707;179444706
Novex-2	13563	40912;40913;40914	chr2:178579981;178579980;178579979	chr2:179444708;179444707;179444706
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-50
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.3389
• 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
I/T	rs777418071	-1.278	0.892	N	0.686	0.244	0.584551062954	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	1.78E-05	0
I/T	rs777418071	-1.278	0.892	N	0.686	0.244	0.584551062954	gnomAD-4.0.0	1.23195E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.34951E-05	3.47858E-05	0
I/V	None	None	0.011	N	0.247	0.116	0.255270683199	gnomAD-4.0.0	1.59233E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8602E-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
I/A	0.3398	likely_benign	0.3142	benign	-1.457	Destabilizing	0.845	D	0.608	neutral	None	None	None	None	I
I/C	0.7274	likely_pathogenic	0.699	pathogenic	-1.11	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
I/D	0.8499	likely_pathogenic	0.8575	pathogenic	-0.284	Destabilizing	0.996	D	0.818	deleterious	None	None	None	None	I
I/E	0.6638	likely_pathogenic	0.6899	pathogenic	-0.286	Destabilizing	0.987	D	0.814	deleterious	None	None	None	None	I
I/F	0.2504	likely_benign	0.2538	benign	-1.018	Destabilizing	0.967	D	0.76	deleterious	N	0.480901438	None	None	I
I/G	0.791	likely_pathogenic	0.7728	pathogenic	-1.753	Destabilizing	0.987	D	0.807	deleterious	None	None	None	None	I
I/H	0.7284	likely_pathogenic	0.7298	pathogenic	-0.786	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	I
I/K	0.4916	ambiguous	0.5338	ambiguous	-0.74	Destabilizing	0.987	D	0.812	deleterious	None	None	None	None	I
I/L	0.1533	likely_benign	0.148	benign	-0.736	Destabilizing	0.426	N	0.324	neutral	N	0.492428351	None	None	I
I/M	0.1376	likely_benign	0.1304	benign	-0.713	Destabilizing	0.983	D	0.755	deleterious	N	0.501799983	None	None	I
I/N	0.4771	ambiguous	0.493	ambiguous	-0.588	Destabilizing	0.994	D	0.822	deleterious	N	0.48135551	None	None	I
I/P	0.6806	likely_pathogenic	0.6475	pathogenic	-0.944	Destabilizing	0.996	D	0.823	deleterious	None	None	None	None	I
I/Q	0.5668	likely_pathogenic	0.5831	pathogenic	-0.752	Destabilizing	0.996	D	0.82	deleterious	None	None	None	None	I
I/R	0.3779	ambiguous	0.4324	ambiguous	-0.188	Destabilizing	0.987	D	0.822	deleterious	None	None	None	None	I
I/S	0.4099	ambiguous	0.4138	ambiguous	-1.321	Destabilizing	0.983	D	0.779	deleterious	N	0.521057747	None	None	I
I/T	0.1803	likely_benign	0.1708	benign	-1.195	Destabilizing	0.892	D	0.686	prob.neutral	N	0.496007374	None	None	I
I/V	0.0868	likely_benign	0.0789	benign	-0.944	Destabilizing	0.011	N	0.247	neutral	N	0.431630608	None	None	I
I/W	0.8593	likely_pathogenic	0.8756	pathogenic	-0.972	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
I/Y	0.6531	likely_pathogenic	0.6837	pathogenic	-0.759	Destabilizing	0.987	D	0.765	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.