TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6750	20473;20474;20475	chr2:178727117;178727116;178727115	chr2:179591844;179591843;179591842
N2AB	6433	19522;19523;19524	chr2:178727117;178727116;178727115	chr2:179591844;179591843;179591842
N2A	5506	16741;16742;16743	chr2:178727117;178727116;178727115	chr2:179591844;179591843;179591842
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-51
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.2968
• 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	rs1560744172	None	0.767	N	0.5	0.311	0.361160317528	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.13E-06	0
S/N	rs1560744172	None	0.767	N	0.5	0.311	0.361160317528	gnomAD-4.0.0	1.65009E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.11857E-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	0.133	likely_benign	0.1352	benign	-0.606	Destabilizing	0.358	N	0.499	neutral	None	None	None	None	N
S/C	0.2947	likely_benign	0.3194	benign	-0.36	Destabilizing	0.091	N	0.438	neutral	D	0.527514061	None	None	N
S/D	0.6515	likely_pathogenic	0.7007	pathogenic	0.368	Stabilizing	0.974	D	0.475	neutral	None	None	None	None	N
S/E	0.7525	likely_pathogenic	0.7936	pathogenic	0.301	Stabilizing	0.962	D	0.469	neutral	None	None	None	None	N
S/F	0.3124	likely_benign	0.3616	ambiguous	-1.062	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
S/G	0.1548	likely_benign	0.1635	benign	-0.76	Destabilizing	0.981	D	0.501	neutral	D	0.526753593	None	None	N
S/H	0.4184	ambiguous	0.4956	ambiguous	-1.173	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
S/I	0.2724	likely_benign	0.3121	benign	-0.324	Destabilizing	0.995	D	0.629	neutral	N	0.500509036	None	None	N
S/K	0.8003	likely_pathogenic	0.8527	pathogenic	-0.47	Destabilizing	0.972	D	0.462	neutral	None	None	None	None	N
S/L	0.2206	likely_benign	0.2342	benign	-0.324	Destabilizing	0.986	D	0.535	neutral	None	None	None	None	N
S/M	0.3631	ambiguous	0.3793	ambiguous	-0.1	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
S/N	0.2044	likely_benign	0.2286	benign	-0.219	Destabilizing	0.767	D	0.5	neutral	N	0.501558993	None	None	N
S/P	0.9022	likely_pathogenic	0.919	pathogenic	-0.388	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	N
S/Q	0.6163	likely_pathogenic	0.6755	pathogenic	-0.43	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
S/R	0.6633	likely_pathogenic	0.73	pathogenic	-0.288	Destabilizing	0.616	D	0.365	neutral	N	0.516089936	None	None	N
S/T	0.1176	likely_benign	0.1221	benign	-0.363	Destabilizing	0.021	N	0.308	neutral	D	0.524917277	None	None	N
S/V	0.2913	likely_benign	0.3098	benign	-0.388	Destabilizing	0.962	D	0.57	neutral	None	None	None	None	N
S/W	0.5442	ambiguous	0.6166	pathogenic	-1.014	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/Y	0.3059	likely_benign	0.3488	ambiguous	-0.755	Destabilizing	0.999	D	0.659	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.