TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32431	97516;97517;97518	chr2:178542465;178542464;178542463	chr2:179407192;179407191;179407190
N2AB	30790	92593;92594;92595	chr2:178542465;178542464;178542463	chr2:179407192;179407191;179407190
N2A	29863	89812;89813;89814	chr2:178542465;178542464;178542463	chr2:179407192;179407191;179407190
N2B	23366	70321;70322;70323	chr2:178542465;178542464;178542463	chr2:179407192;179407191;179407190
Novex-1	23491	70696;70697;70698	chr2:178542465;178542464;178542463	chr2:179407192;179407191;179407190
Novex-2	23558	70897;70898;70899	chr2:178542465;178542464;178542463	chr2:179407192;179407191;179407190
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-124
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.4892
• Predicted PPI site: I

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
P/L	rs1060500426	-0.29	0.27	N	0.509	0.325	0.44349138644	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	1.16144E-04	None	0	0	None	0	None	0	0	0
P/L	rs1060500426	-0.29	0.27	N	0.509	0.325	0.44349138644	gnomAD-4.0.0	7.95834E-06	None	None	None	None	I	None	0	1.14348E-04	None	0	0	None	0	0	0	0	0
P/S	None	None	0.27	N	0.413	0.189	0.188950314367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.0808	likely_benign	0.0677	benign	-0.474	Destabilizing	0.002	N	0.14	neutral	N	0.488342322	None	None	I
P/C	0.5456	ambiguous	0.4428	ambiguous	-0.524	Destabilizing	0.995	D	0.458	neutral	None	None	None	None	I
P/D	0.6125	likely_pathogenic	0.5497	ambiguous	-0.132	Destabilizing	0.329	N	0.445	neutral	None	None	None	None	I
P/E	0.4103	ambiguous	0.3573	ambiguous	-0.246	Destabilizing	0.495	N	0.45	neutral	None	None	None	None	I
P/F	0.5369	ambiguous	0.438	ambiguous	-0.719	Destabilizing	0.944	D	0.482	neutral	None	None	None	None	I
P/G	0.3537	ambiguous	0.2943	benign	-0.615	Destabilizing	0.329	N	0.479	neutral	None	None	None	None	I
P/H	0.2797	likely_benign	0.233	benign	-0.229	Destabilizing	0.944	D	0.463	neutral	None	None	None	None	I
P/I	0.2565	likely_benign	0.2086	benign	-0.254	Destabilizing	0.704	D	0.485	neutral	None	None	None	None	I
P/K	0.4692	ambiguous	0.3934	ambiguous	-0.324	Destabilizing	0.495	N	0.439	neutral	None	None	None	None	I
P/L	0.1347	likely_benign	0.1048	benign	-0.254	Destabilizing	0.27	N	0.509	neutral	N	0.479675854	None	None	I
P/M	0.261	likely_benign	0.2151	benign	-0.255	Destabilizing	0.981	D	0.458	neutral	None	None	None	None	I
P/N	0.3029	likely_benign	0.251	benign	-0.009	Destabilizing	0.013	N	0.153	neutral	None	None	None	None	I
P/Q	0.1938	likely_benign	0.1674	benign	-0.258	Destabilizing	0.784	D	0.492	neutral	N	0.479106763	None	None	I
P/R	0.3725	ambiguous	0.3009	benign	0.163	Stabilizing	0.642	D	0.499	neutral	N	0.466291632	None	None	I
P/S	0.1365	likely_benign	0.1153	benign	-0.405	Destabilizing	0.27	N	0.413	neutral	N	0.506312007	None	None	I
P/T	0.1027	likely_benign	0.0856	benign	-0.415	Destabilizing	0.003	N	0.144	neutral	N	0.472318793	None	None	I
P/V	0.1674	likely_benign	0.1385	benign	-0.292	Destabilizing	0.329	N	0.481	neutral	None	None	None	None	I
P/W	0.76	likely_pathogenic	0.6713	pathogenic	-0.795	Destabilizing	0.995	D	0.484	neutral	None	None	None	None	I
P/Y	0.5212	ambiguous	0.431	ambiguous	-0.48	Destabilizing	0.981	D	0.483	neutral	None	None	None	None	I

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.