TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17595	53008;53009;53010	chr2:178608004;178608003;178608002	chr2:179472731;179472730;179472729
N2AB	15954	48085;48086;48087	chr2:178608004;178608003;178608002	chr2:179472731;179472730;179472729
N2A	15027	45304;45305;45306	chr2:178608004;178608003;178608002	chr2:179472731;179472730;179472729
N2B	8530	25813;25814;25815	chr2:178608004;178608003;178608002	chr2:179472731;179472730;179472729
Novex-1	8655	26188;26189;26190	chr2:178608004;178608003;178608002	chr2:179472731;179472730;179472729
Novex-2	8722	26389;26390;26391	chr2:178608004;178608003;178608002	chr2:179472731;179472730;179472729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-16
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.3147
• 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/V	rs868539342	None	0.081	N	0.316	0.125	0.288727942641	gnomAD-4.0.0	1.59314E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86128E-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	0.4075	ambiguous	0.3828	ambiguous	-1.093	Destabilizing	0.104	N	0.341	neutral	None	None	None	None	I
F/C	0.2427	likely_benign	0.2229	benign	-0.322	Destabilizing	0.946	D	0.337	neutral	N	0.47979741	None	None	I
F/D	0.4404	ambiguous	0.3983	ambiguous	0.848	Stabilizing	None	N	0.129	neutral	None	None	None	None	I
F/E	0.5616	ambiguous	0.5216	ambiguous	0.829	Stabilizing	0.055	N	0.373	neutral	None	None	None	None	I
F/G	0.59	likely_pathogenic	0.5577	ambiguous	-1.3	Destabilizing	0.104	N	0.399	neutral	None	None	None	None	I
F/H	0.3444	ambiguous	0.3208	benign	0.044	Stabilizing	0.497	N	0.353	neutral	None	None	None	None	I
F/I	0.2244	likely_benign	0.2153	benign	-0.565	Destabilizing	0.175	N	0.208	neutral	N	0.443740609	None	None	I
F/K	0.6323	likely_pathogenic	0.587	pathogenic	-0.047	Destabilizing	0.22	N	0.435	neutral	None	None	None	None	I
F/L	0.806	likely_pathogenic	0.7723	pathogenic	-0.565	Destabilizing	0.042	N	0.251	neutral	N	0.477890468	None	None	I
F/M	0.4493	ambiguous	0.4506	ambiguous	-0.318	Destabilizing	0.859	D	0.267	neutral	None	None	None	None	I
F/N	0.3446	ambiguous	0.3043	benign	0.097	Stabilizing	0.22	N	0.447	neutral	None	None	None	None	I
F/P	0.9715	likely_pathogenic	0.9733	pathogenic	-0.721	Destabilizing	0.859	D	0.423	neutral	None	None	None	None	I
F/Q	0.5319	ambiguous	0.4993	ambiguous	-0.012	Destabilizing	0.667	D	0.444	neutral	None	None	None	None	I
F/R	0.52	ambiguous	0.4775	ambiguous	0.455	Stabilizing	0.667	D	0.426	neutral	None	None	None	None	I
F/S	0.2477	likely_benign	0.213	benign	-0.677	Destabilizing	0.175	N	0.379	neutral	N	0.399872402	None	None	I
F/T	0.3359	likely_benign	0.3184	benign	-0.605	Destabilizing	0.364	N	0.43	neutral	None	None	None	None	I
F/V	0.1988	likely_benign	0.1923	benign	-0.721	Destabilizing	0.081	N	0.316	neutral	N	0.43898815	None	None	I
F/W	0.3667	ambiguous	0.3858	ambiguous	-0.349	Destabilizing	0.667	D	0.288	neutral	None	None	None	None	I
F/Y	0.087	likely_benign	0.0836	benign	-0.286	Destabilizing	None	N	0.061	neutral	N	0.352793318	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.