TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30070	90433;90434;90435	chr2:178552692;178552691;178552690	chr2:179417419;179417418;179417417
N2AB	28429	85510;85511;85512	chr2:178552692;178552691;178552690	chr2:179417419;179417418;179417417
N2A	27502	82729;82730;82731	chr2:178552692;178552691;178552690	chr2:179417419;179417418;179417417
N2B	21005	63238;63239;63240	chr2:178552692;178552691;178552690	chr2:179417419;179417418;179417417
Novex-1	21130	63613;63614;63615	chr2:178552692;178552691;178552690	chr2:179417419;179417418;179417417
Novex-2	21197	63814;63815;63816	chr2:178552692;178552691;178552690	chr2:179417419;179417418;179417417
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-107
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1909
• 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
K/R	rs781508633	-0.728	0.046	N	0.161	0.089	0.282575091529	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.30719E-04	None	0	0	0
K/R	rs781508633	-0.728	0.046	N	0.161	0.089	0.282575091529	gnomAD-4.0.0	2.73667E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47794E-05	1.6564E-05

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
K/A	0.7238	likely_pathogenic	0.5665	pathogenic	-1.298	Destabilizing	0.953	D	0.524	neutral	None	None	None	None	N
K/C	0.7082	likely_pathogenic	0.6111	pathogenic	-1.547	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
K/D	0.9704	likely_pathogenic	0.9354	pathogenic	-0.975	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
K/E	0.5461	ambiguous	0.4084	ambiguous	-0.804	Destabilizing	0.939	D	0.424	neutral	N	0.509168672	None	None	N
K/F	0.908	likely_pathogenic	0.8379	pathogenic	-1.082	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
K/G	0.8624	likely_pathogenic	0.7441	pathogenic	-1.67	Destabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	N
K/H	0.5573	ambiguous	0.4559	ambiguous	-1.908	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
K/I	0.6226	likely_pathogenic	0.474	ambiguous	-0.299	Destabilizing	0.991	D	0.831	deleterious	N	0.491260693	None	None	N
K/L	0.5417	ambiguous	0.4035	ambiguous	-0.299	Destabilizing	0.986	D	0.698	prob.neutral	None	None	None	None	N
K/M	0.345	ambiguous	0.2454	benign	-0.446	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
K/N	0.8582	likely_pathogenic	0.7547	pathogenic	-1.08	Destabilizing	0.982	D	0.603	neutral	N	0.473156438	None	None	N
K/P	0.9901	likely_pathogenic	0.9761	pathogenic	-0.607	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
K/Q	0.1808	likely_benign	0.143	benign	-1.145	Destabilizing	0.982	D	0.587	neutral	N	0.493121784	None	None	N
K/R	0.0747	likely_benign	0.0708	benign	-0.738	Destabilizing	0.046	N	0.161	neutral	N	0.416103796	None	None	N
K/S	0.8526	likely_pathogenic	0.7242	pathogenic	-1.816	Destabilizing	0.953	D	0.514	neutral	None	None	None	None	N
K/T	0.6307	likely_pathogenic	0.4523	ambiguous	-1.422	Destabilizing	0.991	D	0.689	prob.neutral	N	0.471092523	None	None	N
K/V	0.6258	likely_pathogenic	0.4814	ambiguous	-0.607	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	N
K/W	0.8963	likely_pathogenic	0.8201	pathogenic	-0.922	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
K/Y	0.826	likely_pathogenic	0.7401	pathogenic	-0.562	Destabilizing	0.998	D	0.815	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.