TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7343	22252;22253;22254	chr2:178722872;178722871;178722870	chr2:179587599;179587598;179587597
N2AB	7026	21301;21302;21303	chr2:178722872;178722871;178722870	chr2:179587599;179587598;179587597
N2A	6099	18520;18521;18522	chr2:178722872;178722871;178722870	chr2:179587599;179587598;179587597
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-58
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5365
• 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
Q/K	rs886043434	None	0.048	N	0.167	0.234	0.190952846119	gnomAD-4.0.0	1.59307E-06	None	None	None	None	I	None	0	0	None	0	2.77932E-05	None	0	0	0	0	0
Q/R	rs1215230781	None	0.744	N	0.402	0.265	0.278968121808	gnomAD-4.0.0	1.59294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86059E-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
Q/A	0.297	likely_benign	0.3953	ambiguous	-0.6	Destabilizing	0.924	D	0.426	neutral	None	None	None	None	I
Q/C	0.6695	likely_pathogenic	0.7899	pathogenic	0.06	Stabilizing	0.999	D	0.511	neutral	None	None	None	None	I
Q/D	0.5105	ambiguous	0.6628	pathogenic	-0.147	Destabilizing	0.012	N	0.167	neutral	None	None	None	None	I
Q/E	0.1095	likely_benign	0.129	benign	-0.107	Destabilizing	0.017	N	0.174	neutral	N	0.385293391	None	None	I
Q/F	0.6862	likely_pathogenic	0.8004	pathogenic	-0.5	Destabilizing	0.992	D	0.525	neutral	None	None	None	None	I
Q/G	0.3827	ambiguous	0.5384	ambiguous	-0.89	Destabilizing	0.961	D	0.497	neutral	None	None	None	None	I
Q/H	0.2051	likely_benign	0.2929	benign	-0.71	Destabilizing	0.995	D	0.454	neutral	N	0.474165956	None	None	I
Q/I	0.4099	ambiguous	0.4944	ambiguous	0.111	Stabilizing	0.136	N	0.401	neutral	None	None	None	None	I
Q/K	0.0995	likely_benign	0.1232	benign	-0.132	Destabilizing	0.048	N	0.167	neutral	N	0.422966345	None	None	I
Q/L	0.1582	likely_benign	0.2245	benign	0.111	Stabilizing	0.647	D	0.472	neutral	N	0.483246799	None	None	I
Q/M	0.4548	ambiguous	0.5337	ambiguous	0.536	Stabilizing	0.988	D	0.459	neutral	None	None	None	None	I
Q/N	0.3674	ambiguous	0.4772	ambiguous	-0.619	Destabilizing	0.899	D	0.373	neutral	None	None	None	None	I
Q/P	0.3446	ambiguous	0.6567	pathogenic	-0.096	Destabilizing	0.976	D	0.506	neutral	N	0.477763622	None	None	I
Q/R	0.1005	likely_benign	0.1349	benign	0.006	Stabilizing	0.744	D	0.402	neutral	N	0.467642629	None	None	I
Q/S	0.3034	likely_benign	0.3847	ambiguous	-0.699	Destabilizing	0.924	D	0.4	neutral	None	None	None	None	I
Q/T	0.2294	likely_benign	0.2827	benign	-0.469	Destabilizing	0.699	D	0.471	neutral	None	None	None	None	I
Q/V	0.2966	likely_benign	0.367	ambiguous	-0.096	Destabilizing	0.422	N	0.471	neutral	None	None	None	None	I
Q/W	0.5572	ambiguous	0.7448	pathogenic	-0.356	Destabilizing	1.0	D	0.536	neutral	None	None	None	None	I
Q/Y	0.4775	ambiguous	0.6261	pathogenic	-0.147	Destabilizing	0.997	D	0.527	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.