TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22901	68926;68927;68928	chr2:178577725;178577724;178577723	chr2:179442452;179442451;179442450
N2AB	21260	64003;64004;64005	chr2:178577725;178577724;178577723	chr2:179442452;179442451;179442450
N2A	20333	61222;61223;61224	chr2:178577725;178577724;178577723	chr2:179442452;179442451;179442450
N2B	13836	41731;41732;41733	chr2:178577725;178577724;178577723	chr2:179442452;179442451;179442450
Novex-1	13961	42106;42107;42108	chr2:178577725;178577724;178577723	chr2:179442452;179442451;179442450
Novex-2	14028	42307;42308;42309	chr2:178577725;178577724;178577723	chr2:179442452;179442451;179442450
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-54
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.2317
• 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
F/Y	None	None	None	N	0.16	0.091	None	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85958E-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
F/A	0.9557	likely_pathogenic	0.9569	pathogenic	-2.305	Highly Destabilizing	0.241	N	0.513	neutral	None	None	None	None	I
F/C	0.7437	likely_pathogenic	0.7359	pathogenic	-1.495	Destabilizing	0.975	D	0.585	neutral	N	0.519020306	None	None	I
F/D	0.9888	likely_pathogenic	0.99	pathogenic	-1.674	Destabilizing	0.818	D	0.6	neutral	None	None	None	None	I
F/E	0.9906	likely_pathogenic	0.9915	pathogenic	-1.528	Destabilizing	0.818	D	0.595	neutral	None	None	None	None	I
F/G	0.9773	likely_pathogenic	0.9776	pathogenic	-2.695	Highly Destabilizing	0.563	D	0.552	neutral	None	None	None	None	I
F/H	0.8689	likely_pathogenic	0.8734	pathogenic	-0.956	Destabilizing	0.69	D	0.51	neutral	None	None	None	None	I
F/I	0.8035	likely_pathogenic	0.8131	pathogenic	-1.096	Destabilizing	0.193	N	0.459	neutral	N	0.477382719	None	None	I
F/K	0.9864	likely_pathogenic	0.9876	pathogenic	-1.726	Destabilizing	0.69	D	0.594	neutral	None	None	None	None	I
F/L	0.9679	likely_pathogenic	0.9663	pathogenic	-1.096	Destabilizing	0.09	N	0.449	neutral	N	0.505626935	None	None	I
F/M	0.8608	likely_pathogenic	0.8583	pathogenic	-0.838	Destabilizing	0.818	D	0.416	neutral	None	None	None	None	I
F/N	0.9673	likely_pathogenic	0.968	pathogenic	-2.027	Highly Destabilizing	0.818	D	0.602	neutral	None	None	None	None	I
F/P	0.9997	likely_pathogenic	0.9997	pathogenic	-1.498	Destabilizing	0.932	D	0.625	neutral	None	None	None	None	I
F/Q	0.9752	likely_pathogenic	0.9761	pathogenic	-2.004	Highly Destabilizing	0.818	D	0.616	neutral	None	None	None	None	I
F/R	0.9699	likely_pathogenic	0.9715	pathogenic	-1.145	Destabilizing	0.818	D	0.604	neutral	None	None	None	None	I
F/S	0.9223	likely_pathogenic	0.921	pathogenic	-2.77	Highly Destabilizing	0.324	N	0.546	neutral	N	0.504173934	None	None	I
F/T	0.9602	likely_pathogenic	0.963	pathogenic	-2.519	Highly Destabilizing	0.388	N	0.487	neutral	None	None	None	None	I
F/V	0.7478	likely_pathogenic	0.7543	pathogenic	-1.498	Destabilizing	0.001	N	0.294	neutral	N	0.511550042	None	None	I
F/W	0.7498	likely_pathogenic	0.7547	pathogenic	-0.188	Destabilizing	0.818	D	0.433	neutral	None	None	None	None	I
F/Y	0.2162	likely_benign	0.2108	benign	-0.489	Destabilizing	None	N	0.16	neutral	N	0.414292854	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.