TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27833	83722;83723;83724	chr2:178562635;178562634;178562633	chr2:179427362;179427361;179427360
N2AB	26192	78799;78800;78801	chr2:178562635;178562634;178562633	chr2:179427362;179427361;179427360
N2A	25265	76018;76019;76020	chr2:178562635;178562634;178562633	chr2:179427362;179427361;179427360
N2B	18768	56527;56528;56529	chr2:178562635;178562634;178562633	chr2:179427362;179427361;179427360
Novex-1	18893	56902;56903;56904	chr2:178562635;178562634;178562633	chr2:179427362;179427361;179427360
Novex-2	18960	57103;57104;57105	chr2:178562635;178562634;178562633	chr2:179427362;179427361;179427360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-90
• Domain position: 68
• Structural Position: 100
• Q(SASA): 0.3825
• 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
G/R	None	None	0.999	D	0.881	0.562	0.794854992122	gnomAD-4.0.0	3.44414E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50988E-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
G/A	0.5077	ambiguous	0.6231	pathogenic	-0.368	Destabilizing	0.978	D	0.725	prob.delet.	N	0.495965316	None	None	N
G/C	0.6876	likely_pathogenic	0.798	pathogenic	-0.884	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/D	0.6913	likely_pathogenic	0.8462	pathogenic	-0.576	Destabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
G/E	0.7854	likely_pathogenic	0.9099	pathogenic	-0.737	Destabilizing	0.999	D	0.867	deleterious	N	0.51242373	None	None	N
G/F	0.9427	likely_pathogenic	0.9701	pathogenic	-1.032	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
G/H	0.8757	likely_pathogenic	0.9389	pathogenic	-0.584	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/I	0.9063	likely_pathogenic	0.9645	pathogenic	-0.464	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
G/K	0.915	likely_pathogenic	0.9645	pathogenic	-0.866	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
G/L	0.9166	likely_pathogenic	0.951	pathogenic	-0.464	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
G/M	0.9028	likely_pathogenic	0.9505	pathogenic	-0.456	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/N	0.5434	ambiguous	0.6437	pathogenic	-0.492	Destabilizing	0.707	D	0.665	neutral	None	None	None	None	N
G/P	0.9886	likely_pathogenic	0.9952	pathogenic	-0.398	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
G/Q	0.829	likely_pathogenic	0.9144	pathogenic	-0.797	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
G/R	0.8732	likely_pathogenic	0.9429	pathogenic	-0.391	Destabilizing	0.999	D	0.881	deleterious	D	0.52717385	None	None	N
G/S	0.2905	likely_benign	0.3868	ambiguous	-0.667	Destabilizing	0.99	D	0.787	deleterious	None	None	None	None	N
G/T	0.6122	likely_pathogenic	0.7526	pathogenic	-0.759	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
G/V	0.832	likely_pathogenic	0.9247	pathogenic	-0.398	Destabilizing	0.999	D	0.875	deleterious	N	0.521186369	None	None	N
G/W	0.9029	likely_pathogenic	0.9564	pathogenic	-1.175	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/Y	0.8778	likely_pathogenic	0.9373	pathogenic	-0.831	Destabilizing	1.0	D	0.87	deleterious	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.