TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7633	23122;23123;23124	chr2:178721122;178721121;178721120	chr2:179585849;179585848;179585847
N2AB	7316	22171;22172;22173	chr2:178721122;178721121;178721120	chr2:179585849;179585848;179585847
N2A	6389	19390;19391;19392	chr2:178721122;178721121;178721120	chr2:179585849;179585848;179585847
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-61
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.3249
• 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	rs1247821028	None	0.051	N	0.143	0.158	0.211220785272	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-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
S/A	0.087	likely_benign	0.0969	benign	-0.273	Destabilizing	0.525	D	0.267	neutral	None	None	None	None	N
S/C	0.2271	likely_benign	0.2856	benign	-0.349	Destabilizing	0.997	D	0.32	neutral	N	0.493863219	None	None	N
S/D	0.714	likely_pathogenic	0.7759	pathogenic	0.559	Stabilizing	0.728	D	0.301	neutral	None	None	None	None	N
S/E	0.7852	likely_pathogenic	0.8443	pathogenic	0.539	Stabilizing	0.842	D	0.313	neutral	None	None	None	None	N
S/F	0.2569	likely_benign	0.3155	benign	-0.687	Destabilizing	0.974	D	0.41	neutral	None	None	None	None	N
S/G	0.1014	likely_benign	0.1185	benign	-0.465	Destabilizing	0.005	N	0.091	neutral	N	0.476110183	None	None	N
S/H	0.5456	ambiguous	0.6306	pathogenic	-0.826	Destabilizing	0.974	D	0.335	neutral	None	None	None	None	N
S/I	0.2007	likely_benign	0.2356	benign	0.111	Stabilizing	0.934	D	0.392	neutral	N	0.502352635	None	None	N
S/K	0.8642	likely_pathogenic	0.9116	pathogenic	-0.203	Destabilizing	0.067	N	0.129	neutral	None	None	None	None	N
S/L	0.1052	likely_benign	0.1206	benign	0.111	Stabilizing	0.728	D	0.385	neutral	None	None	None	None	N
S/M	0.2291	likely_benign	0.2538	benign	-0.012	Destabilizing	0.991	D	0.331	neutral	None	None	None	None	N
S/N	0.2356	likely_benign	0.2636	benign	-0.189	Destabilizing	0.051	N	0.143	neutral	N	0.516167294	None	None	N
S/P	0.887	likely_pathogenic	0.9014	pathogenic	0.017	Stabilizing	0.974	D	0.369	neutral	None	None	None	None	N
S/Q	0.6755	likely_pathogenic	0.7603	pathogenic	-0.244	Destabilizing	0.949	D	0.367	neutral	None	None	None	None	N
S/R	0.7641	likely_pathogenic	0.8458	pathogenic	-0.162	Destabilizing	0.669	D	0.359	neutral	N	0.504699507	None	None	N
S/T	0.0856	likely_benign	0.0904	benign	-0.233	Destabilizing	0.022	N	0.095	neutral	N	0.417464524	None	None	N
S/V	0.2343	likely_benign	0.267	benign	0.017	Stabilizing	0.728	D	0.368	neutral	None	None	None	None	N
S/W	0.4842	ambiguous	0.6065	pathogenic	-0.751	Destabilizing	0.998	D	0.479	neutral	None	None	None	None	N
S/Y	0.3138	likely_benign	0.3987	ambiguous	-0.402	Destabilizing	0.991	D	0.408	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.