TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9610	29053;29054;29055	chr2:178707739;178707738;178707737	chr2:179572466;179572465;179572464
N2AB	9293	28102;28103;28104	chr2:178707739;178707738;178707737	chr2:179572466;179572465;179572464
N2A	8366	25321;25322;25323	chr2:178707739;178707738;178707737	chr2:179572466;179572465;179572464
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-82
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.338
• Predicted PPI site: N

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/N	rs371759532	-0.597	0.062	None	0.455	0.09	None	gnomAD-2.1.1	7.49E-05	None	None	None	None	N	None	8.67912E-04	0	None	0	0	None	0	None	0	0	0
S/N	rs371759532	-0.597	0.062	None	0.455	0.09	None	gnomAD-3.1.2	1.97055E-04	None	None	None	None	N	None	7.2338E-04	0	0	0	0	None	0	0	0	0	0
S/N	rs371759532	-0.597	0.062	None	0.455	0.09	None	gnomAD-4.0.0	3.408E-05	None	None	None	None	N	None	7.20519E-04	0	None	0	0	None	0	0	0	0	1.60108E-05

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	0.0921	likely_benign	0.0926	benign	-0.768	Destabilizing	0.035	N	0.437	neutral	None	None	None	None	N
S/C	0.1559	likely_benign	0.1759	benign	-0.557	Destabilizing	0.78	D	0.541	neutral	None	None	None	None	N
S/D	0.4601	ambiguous	0.4863	ambiguous	-0.611	Destabilizing	0.149	N	0.426	neutral	None	None	None	None	N
S/E	0.5112	ambiguous	0.5745	pathogenic	-0.557	Destabilizing	0.149	N	0.444	neutral	None	None	None	None	N
S/F	0.1958	likely_benign	0.1897	benign	-0.771	Destabilizing	0.38	N	0.593	neutral	None	None	None	None	N
S/G	0.1076	likely_benign	0.1033	benign	-1.08	Destabilizing	None	N	0.23	neutral	None	None	None	None	N
S/H	0.2662	likely_benign	0.3031	benign	-1.559	Destabilizing	0.001	N	0.409	neutral	None	None	None	None	N
S/I	0.1594	likely_benign	0.1697	benign	-0.029	Destabilizing	0.188	N	0.585	neutral	None	None	None	None	N
S/K	0.4988	ambiguous	0.588	pathogenic	-0.705	Destabilizing	0.002	N	0.323	neutral	None	None	None	None	N
S/L	0.1284	likely_benign	0.1193	benign	-0.029	Destabilizing	0.081	N	0.511	neutral	None	None	None	None	N
S/M	0.2522	likely_benign	0.2619	benign	0.126	Stabilizing	0.824	D	0.532	neutral	None	None	None	None	N
S/N	0.1485	likely_benign	0.1594	benign	-0.833	Destabilizing	0.062	N	0.455	neutral	None	None	None	None	N
S/P	0.6614	likely_pathogenic	0.5864	pathogenic	-0.24	Destabilizing	0.555	D	0.558	neutral	None	None	None	None	N
S/Q	0.4136	ambiguous	0.4699	ambiguous	-0.872	Destabilizing	0.38	N	0.497	neutral	None	None	None	None	N
S/R	0.3737	ambiguous	0.429	ambiguous	-0.733	Destabilizing	0.001	N	0.356	neutral	None	None	None	None	N
S/T	0.0838	likely_benign	0.0904	benign	-0.741	Destabilizing	None	N	0.338	neutral	None	None	None	None	N
S/V	0.1888	likely_benign	0.2018	benign	-0.24	Destabilizing	0.081	N	0.558	neutral	None	None	None	None	N
S/W	0.3983	ambiguous	0.3755	ambiguous	-0.816	Destabilizing	0.935	D	0.632	neutral	None	None	None	None	N
S/Y	0.1998	likely_benign	0.1986	benign	-0.513	Destabilizing	0.235	N	0.581	neutral	None	None	None	None	N

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.