TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25822	77689;77690;77691	chr2:178568668;178568667;178568666	chr2:179433395;179433394;179433393
N2AB	24181	72766;72767;72768	chr2:178568668;178568667;178568666	chr2:179433395;179433394;179433393
N2A	23254	69985;69986;69987	chr2:178568668;178568667;178568666	chr2:179433395;179433394;179433393
N2B	16757	50494;50495;50496	chr2:178568668;178568667;178568666	chr2:179433395;179433394;179433393
Novex-1	16882	50869;50870;50871	chr2:178568668;178568667;178568666	chr2:179433395;179433394;179433393
Novex-2	16949	51070;51071;51072	chr2:178568668;178568667;178568666	chr2:179433395;179433394;179433393
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-136
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4599
• 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/P	None	None	0.896	N	0.354	0.443	0.32082282376	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85956E-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	0.0624	likely_benign	0.0674	benign	-0.416	Destabilizing	0.001	N	0.079	neutral	N	0.498061536	None	None	N
S/C	0.0854	likely_benign	0.0903	benign	-0.314	Destabilizing	0.97	D	0.29	neutral	D	0.532375907	None	None	N
S/D	0.4231	ambiguous	0.4608	ambiguous	0.007	Stabilizing	0.617	D	0.297	neutral	None	None	None	None	N
S/E	0.4255	ambiguous	0.4882	ambiguous	-0.044	Destabilizing	0.447	N	0.233	neutral	None	None	None	None	N
S/F	0.116	likely_benign	0.1135	benign	-0.771	Destabilizing	0.681	D	0.399	neutral	D	0.533926336	None	None	N
S/G	0.0988	likely_benign	0.1019	benign	-0.608	Destabilizing	0.25	N	0.307	neutral	None	None	None	None	N
S/H	0.2359	likely_benign	0.253	benign	-1.136	Destabilizing	0.92	D	0.308	neutral	None	None	None	None	N
S/I	0.1023	likely_benign	0.1055	benign	-0.033	Destabilizing	0.85	D	0.392	neutral	None	None	None	None	N
S/K	0.4248	ambiguous	0.473	ambiguous	-0.636	Destabilizing	0.005	N	0.094	neutral	None	None	None	None	N
S/L	0.0703	likely_benign	0.072	benign	-0.033	Destabilizing	0.447	N	0.361	neutral	None	None	None	None	N
S/M	0.1218	likely_benign	0.1269	benign	0.147	Stabilizing	0.972	D	0.299	neutral	None	None	None	None	N
S/N	0.1392	likely_benign	0.1393	benign	-0.411	Destabilizing	0.617	D	0.329	neutral	None	None	None	None	N
S/P	0.7723	likely_pathogenic	0.8253	pathogenic	-0.128	Destabilizing	0.896	D	0.354	neutral	N	0.513764673	None	None	N
S/Q	0.3342	likely_benign	0.3766	ambiguous	-0.591	Destabilizing	0.85	D	0.327	neutral	None	None	None	None	N
S/R	0.3439	ambiguous	0.3749	ambiguous	-0.488	Destabilizing	0.447	N	0.329	neutral	None	None	None	None	N
S/T	0.066	likely_benign	0.066	benign	-0.448	Destabilizing	0.334	N	0.303	neutral	N	0.489113979	None	None	N
S/V	0.1065	likely_benign	0.1162	benign	-0.128	Destabilizing	0.447	N	0.347	neutral	None	None	None	None	N
S/W	0.2311	likely_benign	0.2477	benign	-0.787	Destabilizing	0.992	D	0.414	neutral	None	None	None	None	N
S/Y	0.1286	likely_benign	0.1309	benign	-0.515	Destabilizing	0.016	N	0.276	neutral	N	0.499775021	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.