TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26319	79180;79181;79182	chr2:178567177;178567176;178567175	chr2:179431904;179431903;179431902
N2AB	24678	74257;74258;74259	chr2:178567177;178567176;178567175	chr2:179431904;179431903;179431902
N2A	23751	71476;71477;71478	chr2:178567177;178567176;178567175	chr2:179431904;179431903;179431902
N2B	17254	51985;51986;51987	chr2:178567177;178567176;178567175	chr2:179431904;179431903;179431902
Novex-1	17379	52360;52361;52362	chr2:178567177;178567176;178567175	chr2:179431904;179431903;179431902
Novex-2	17446	52561;52562;52563	chr2:178567177;178567176;178567175	chr2:179431904;179431903;179431902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-79
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2056
• 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
I/N	None	None	0.999	D	0.845	0.603	0.862726850884	gnomAD-4.0.0	6.84407E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99688E-07	0	0
I/T	rs1706219374	None	0.989	D	0.786	0.574	0.726705045765	gnomAD-4.0.0	2.05322E-06	None	None	None	None	I	None	0	6.71111E-05	None	0	0	None	0	0	0	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
I/A	0.9651	likely_pathogenic	0.9669	pathogenic	-2.32	Highly Destabilizing	0.992	D	0.671	neutral	None	None	None	None	I
I/C	0.96	likely_pathogenic	0.9607	pathogenic	-1.459	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
I/D	0.9987	likely_pathogenic	0.9987	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
I/E	0.9971	likely_pathogenic	0.9972	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
I/F	0.9129	likely_pathogenic	0.8978	pathogenic	-1.69	Destabilizing	0.998	D	0.756	deleterious	D	0.536222296	None	None	I
I/G	0.9954	likely_pathogenic	0.9958	pathogenic	-2.729	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
I/H	0.9959	likely_pathogenic	0.9957	pathogenic	-2.013	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
I/K	0.9918	likely_pathogenic	0.9912	pathogenic	-1.683	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
I/L	0.433	ambiguous	0.4014	ambiguous	-1.211	Destabilizing	0.889	D	0.437	neutral	N	0.490783848	None	None	I
I/M	0.6581	likely_pathogenic	0.6323	pathogenic	-0.85	Destabilizing	0.998	D	0.717	prob.delet.	D	0.545505141	None	None	I
I/N	0.9747	likely_pathogenic	0.9757	pathogenic	-1.621	Destabilizing	0.999	D	0.845	deleterious	D	0.53977115	None	None	I
I/P	0.9781	likely_pathogenic	0.9812	pathogenic	-1.554	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
I/Q	0.9951	likely_pathogenic	0.995	pathogenic	-1.753	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
I/R	0.9864	likely_pathogenic	0.9861	pathogenic	-1.071	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
I/S	0.9716	likely_pathogenic	0.9747	pathogenic	-2.262	Highly Destabilizing	0.998	D	0.819	deleterious	D	0.539010681	None	None	I
I/T	0.9145	likely_pathogenic	0.915	pathogenic	-2.072	Highly Destabilizing	0.989	D	0.786	deleterious	D	0.52502103	None	None	I
I/V	0.0947	likely_benign	0.0941	benign	-1.554	Destabilizing	0.333	N	0.258	neutral	N	0.480774136	None	None	I
I/W	0.9984	likely_pathogenic	0.9981	pathogenic	-1.886	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
I/Y	0.9887	likely_pathogenic	0.9879	pathogenic	-1.664	Destabilizing	1.0	D	0.789	deleterious	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.