TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18290	55093;55094;55095	chr2:178602534;178602533;178602532	chr2:179467261;179467260;179467259
N2AB	16649	50170;50171;50172	chr2:178602534;178602533;178602532	chr2:179467261;179467260;179467259
N2A	15722	47389;47390;47391	chr2:178602534;178602533;178602532	chr2:179467261;179467260;179467259
N2B	9225	27898;27899;27900	chr2:178602534;178602533;178602532	chr2:179467261;179467260;179467259
Novex-1	9350	28273;28274;28275	chr2:178602534;178602533;178602532	chr2:179467261;179467260;179467259
Novex-2	9417	28474;28475;28476	chr2:178602534;178602533;178602532	chr2:179467261;179467260;179467259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-21
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1507
• 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/L	None	None	0.062	N	0.567	0.317	0.426551566703	gnomAD-4.0.0	1.62226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9099E-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	0.1436	likely_benign	0.1058	benign	-0.698	Destabilizing	None	N	0.275	neutral	N	0.502685417	None	None	N
S/C	0.1387	likely_benign	0.1157	benign	-0.632	Destabilizing	0.824	D	0.585	neutral	None	None	None	None	N
S/D	0.666	likely_pathogenic	0.539	ambiguous	-0.691	Destabilizing	0.149	N	0.541	neutral	None	None	None	None	N
S/E	0.7493	likely_pathogenic	0.6333	pathogenic	-0.659	Destabilizing	0.149	N	0.543	neutral	None	None	None	None	N
S/F	0.2914	likely_benign	0.169	benign	-0.768	Destabilizing	0.555	D	0.627	neutral	None	None	None	None	N
S/G	0.2339	likely_benign	0.1582	benign	-0.979	Destabilizing	0.035	N	0.487	neutral	None	None	None	None	N
S/H	0.4146	ambiguous	0.3303	benign	-1.447	Destabilizing	0.935	D	0.585	neutral	None	None	None	None	N
S/I	0.2377	likely_benign	0.1545	benign	-0.05	Destabilizing	0.235	N	0.611	neutral	None	None	None	None	N
S/K	0.8352	likely_pathogenic	0.7289	pathogenic	-0.747	Destabilizing	0.149	N	0.535	neutral	None	None	None	None	N
S/L	0.1394	likely_benign	0.0988	benign	-0.05	Destabilizing	0.062	N	0.567	neutral	N	0.474152021	None	None	N
S/M	0.2447	likely_benign	0.1791	benign	0.178	Stabilizing	0.555	D	0.591	neutral	None	None	None	None	N
S/N	0.2888	likely_benign	0.1939	benign	-0.855	Destabilizing	0.149	N	0.567	neutral	None	None	None	None	N
S/P	0.9277	likely_pathogenic	0.8567	pathogenic	-0.231	Destabilizing	0.484	N	0.592	neutral	N	0.486981505	None	None	N
S/Q	0.6646	likely_pathogenic	0.5388	ambiguous	-0.982	Destabilizing	0.555	D	0.577	neutral	None	None	None	None	N
S/R	0.7656	likely_pathogenic	0.6443	pathogenic	-0.686	Destabilizing	0.38	N	0.606	neutral	None	None	None	None	N
S/T	0.0796	likely_benign	0.0625	benign	-0.794	Destabilizing	None	N	0.28	neutral	N	0.437132429	None	None	N
S/V	0.244	likely_benign	0.1656	benign	-0.231	Destabilizing	0.081	N	0.567	neutral	None	None	None	None	N
S/W	0.4515	ambiguous	0.3693	ambiguous	-0.781	Destabilizing	0.935	D	0.675	neutral	None	None	None	None	N
S/Y	0.2563	likely_benign	0.1854	benign	-0.487	Destabilizing	0.555	D	0.615	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.