TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30847	92764;92765;92766	chr2:178549087;178549086;178549085	chr2:179413814;179413813;179413812
N2AB	29206	87841;87842;87843	chr2:178549087;178549086;178549085	chr2:179413814;179413813;179413812
N2A	28279	85060;85061;85062	chr2:178549087;178549086;178549085	chr2:179413814;179413813;179413812
N2B	21782	65569;65570;65571	chr2:178549087;178549086;178549085	chr2:179413814;179413813;179413812
Novex-1	21907	65944;65945;65946	chr2:178549087;178549086;178549085	chr2:179413814;179413813;179413812
Novex-2	21974	66145;66146;66147	chr2:178549087;178549086;178549085	chr2:179413814;179413813;179413812
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: Fn3-113
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5103
• 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/S	rs906140300	None	0.942	N	0.602	0.368	0.473065174198	gnomAD-4.0.0	2.05255E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.6983E-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	0.5175	ambiguous	0.5421	ambiguous	-1.045	Destabilizing	0.86	D	0.493	neutral	None	None	None	None	I
F/C	0.3976	ambiguous	0.3761	ambiguous	-0.295	Destabilizing	0.997	D	0.623	neutral	N	0.473388725	None	None	I
F/D	0.69	likely_pathogenic	0.7238	pathogenic	0.816	Stabilizing	0.993	D	0.661	neutral	None	None	None	None	I
F/E	0.7971	likely_pathogenic	0.8178	pathogenic	0.794	Stabilizing	0.978	D	0.662	neutral	None	None	None	None	I
F/G	0.733	likely_pathogenic	0.7486	pathogenic	-1.246	Destabilizing	0.978	D	0.643	neutral	None	None	None	None	I
F/H	0.5399	ambiguous	0.5252	ambiguous	0.146	Stabilizing	0.956	D	0.572	neutral	None	None	None	None	I
F/I	0.3867	ambiguous	0.39	ambiguous	-0.536	Destabilizing	0.942	D	0.515	neutral	N	0.456629761	None	None	I
F/K	0.8473	likely_pathogenic	0.8562	pathogenic	-0.089	Destabilizing	0.956	D	0.666	neutral	None	None	None	None	I
F/L	0.899	likely_pathogenic	0.9039	pathogenic	-0.536	Destabilizing	0.698	D	0.47	neutral	N	0.466980041	None	None	I
F/M	0.5909	likely_pathogenic	0.6004	pathogenic	-0.35	Destabilizing	0.998	D	0.534	neutral	None	None	None	None	I
F/N	0.5583	ambiguous	0.5745	pathogenic	0.009	Stabilizing	0.978	D	0.669	neutral	None	None	None	None	I
F/P	0.9835	likely_pathogenic	0.9868	pathogenic	-0.686	Destabilizing	0.993	D	0.655	neutral	None	None	None	None	I
F/Q	0.7316	likely_pathogenic	0.7379	pathogenic	-0.075	Destabilizing	0.978	D	0.658	neutral	None	None	None	None	I
F/R	0.711	likely_pathogenic	0.7367	pathogenic	0.411	Stabilizing	0.978	D	0.663	neutral	None	None	None	None	I
F/S	0.3242	likely_benign	0.3486	ambiguous	-0.717	Destabilizing	0.942	D	0.602	neutral	N	0.382246646	None	None	I
F/T	0.4529	ambiguous	0.4802	ambiguous	-0.649	Destabilizing	0.978	D	0.608	neutral	None	None	None	None	I
F/V	0.3587	ambiguous	0.3603	ambiguous	-0.686	Destabilizing	0.822	D	0.549	neutral	N	0.453589456	None	None	I
F/W	0.4821	ambiguous	0.4819	ambiguous	-0.302	Destabilizing	0.994	D	0.524	neutral	None	None	None	None	I
F/Y	0.1376	likely_benign	0.1311	benign	-0.281	Destabilizing	0.014	N	0.265	neutral	N	0.3163898	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.