TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14665	44218;44219;44220	chr2:178631055;178631054;178631053	chr2:179495782;179495781;179495780
N2AB	13024	39295;39296;39297	chr2:178631055;178631054;178631053	chr2:179495782;179495781;179495780
N2A	12097	36514;36515;36516	chr2:178631055;178631054;178631053	chr2:179495782;179495781;179495780
N2B	5600	17023;17024;17025	chr2:178631055;178631054;178631053	chr2:179495782;179495781;179495780
Novex-1	5725	17398;17399;17400	chr2:178631055;178631054;178631053	chr2:179495782;179495781;179495780
Novex-2	5792	17599;17600;17601	chr2:178631055;178631054;178631053	chr2:179495782;179495781;179495780
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: Ig-97
• Domain position: 80
• Structural Position: 171
• Q(SASA): 0.4233
• 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/A	None	None	0.022	N	0.224	0.065	0.141422826196	gnomAD-4.0.0	2.73805E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59853E-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	0.0768	likely_benign	0.0863	benign	-0.661	Destabilizing	0.022	N	0.224	neutral	N	0.447143358	None	None	N
S/C	0.1592	likely_benign	0.1873	benign	-0.427	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
S/D	0.4622	ambiguous	0.5016	ambiguous	-0.116	Destabilizing	0.915	D	0.527	neutral	None	None	None	None	N
S/E	0.445	ambiguous	0.4793	ambiguous	-0.168	Destabilizing	0.915	D	0.511	neutral	None	None	None	None	N
S/F	0.1729	likely_benign	0.1898	benign	-1.076	Destabilizing	0.949	D	0.592	neutral	None	None	None	None	N
S/G	0.161	likely_benign	0.174	benign	-0.836	Destabilizing	0.728	D	0.537	neutral	None	None	None	None	N
S/H	0.4226	ambiguous	0.4461	ambiguous	-1.383	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
S/I	0.1504	likely_benign	0.1682	benign	-0.312	Destabilizing	0.904	D	0.569	neutral	None	None	None	None	N
S/K	0.6695	likely_pathogenic	0.7031	pathogenic	-0.573	Destabilizing	0.842	D	0.515	neutral	None	None	None	None	N
S/L	0.1116	likely_benign	0.1257	benign	-0.312	Destabilizing	0.223	N	0.523	neutral	D	0.53936587	None	None	N
S/M	0.2216	likely_benign	0.2254	benign	0.105	Stabilizing	0.525	D	0.384	neutral	None	None	None	None	N
S/N	0.1993	likely_benign	0.2126	benign	-0.395	Destabilizing	0.915	D	0.538	neutral	None	None	None	None	N
S/P	0.7553	likely_pathogenic	0.8375	pathogenic	-0.398	Destabilizing	0.966	D	0.563	neutral	D	0.632743051	None	None	N
S/Q	0.5561	ambiguous	0.5693	pathogenic	-0.681	Destabilizing	0.974	D	0.577	neutral	None	None	None	None	N
S/R	0.5475	ambiguous	0.5871	pathogenic	-0.395	Destabilizing	0.974	D	0.567	neutral	None	None	None	None	N
S/T	0.0805	likely_benign	0.0806	benign	-0.502	Destabilizing	0.051	N	0.289	neutral	N	0.448909774	None	None	N
S/V	0.1655	likely_benign	0.1801	benign	-0.398	Destabilizing	0.728	D	0.525	neutral	None	None	None	None	N
S/W	0.3235	likely_benign	0.3727	ambiguous	-1.008	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
S/Y	0.177	likely_benign	0.2029	benign	-0.75	Destabilizing	0.974	D	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.