TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30123	90592;90593;90594	chr2:178552533;178552532;178552531	chr2:179417260;179417259;179417258
N2AB	28482	85669;85670;85671	chr2:178552533;178552532;178552531	chr2:179417260;179417259;179417258
N2A	27555	82888;82889;82890	chr2:178552533;178552532;178552531	chr2:179417260;179417259;179417258
N2B	21058	63397;63398;63399	chr2:178552533;178552532;178552531	chr2:179417260;179417259;179417258
Novex-1	21183	63772;63773;63774	chr2:178552533;178552532;178552531	chr2:179417260;179417259;179417258
Novex-2	21250	63973;63974;63975	chr2:178552533;178552532;178552531	chr2:179417260;179417259;179417258
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: 94
• Structural Position: 131
• Q(SASA): 0.4787
• 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/E	rs777314679	0.335	0.92	N	0.455	0.204	0.253205268125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/E	rs777314679	0.335	0.92	N	0.455	0.204	0.253205268125	gnomAD-4.0.0	1.36848E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79893E-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
K/A	0.6867	likely_pathogenic	0.5672	pathogenic	-0.233	Destabilizing	0.968	D	0.498	neutral	None	None	None	None	N
K/C	0.8452	likely_pathogenic	0.7889	pathogenic	-0.359	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/D	0.8695	likely_pathogenic	0.7923	pathogenic	0.173	Stabilizing	0.991	D	0.449	neutral	None	None	None	None	N
K/E	0.3502	ambiguous	0.2387	benign	0.22	Stabilizing	0.92	D	0.455	neutral	N	0.512320834	None	None	N
K/F	0.9498	likely_pathogenic	0.9256	pathogenic	-0.211	Destabilizing	0.991	D	0.849	deleterious	None	None	None	None	N
K/G	0.7663	likely_pathogenic	0.6695	pathogenic	-0.518	Destabilizing	0.995	D	0.537	neutral	None	None	None	None	N
K/H	0.5083	ambiguous	0.4454	ambiguous	-0.852	Destabilizing	0.999	D	0.469	neutral	None	None	None	None	N
K/I	0.7294	likely_pathogenic	0.6462	pathogenic	0.46	Stabilizing	0.976	D	0.825	deleterious	N	0.519438807	None	None	N
K/L	0.7047	likely_pathogenic	0.618	pathogenic	0.46	Stabilizing	0.939	D	0.545	neutral	None	None	None	None	N
K/M	0.4642	ambiguous	0.3775	ambiguous	0.354	Stabilizing	0.863	D	0.424	neutral	None	None	None	None	N
K/N	0.745	likely_pathogenic	0.6217	pathogenic	0.013	Stabilizing	0.994	D	0.459	neutral	N	0.479265142	None	None	N
K/P	0.984	likely_pathogenic	0.9727	pathogenic	0.26	Stabilizing	0.998	D	0.517	neutral	None	None	None	None	N
K/Q	0.181	likely_benign	0.1376	benign	-0.171	Destabilizing	0.675	D	0.2	neutral	N	0.484248798	None	None	N
K/R	0.0985	likely_benign	0.0922	benign	-0.236	Destabilizing	0.958	D	0.465	neutral	N	0.486382239	None	None	N
K/S	0.7044	likely_pathogenic	0.5736	pathogenic	-0.629	Destabilizing	0.968	D	0.457	neutral	None	None	None	None	N
K/T	0.3605	ambiguous	0.2645	benign	-0.401	Destabilizing	0.994	D	0.447	neutral	N	0.459307101	None	None	N
K/V	0.6585	likely_pathogenic	0.573	pathogenic	0.26	Stabilizing	0.939	D	0.548	neutral	None	None	None	None	N
K/W	0.9097	likely_pathogenic	0.8874	pathogenic	-0.103	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
K/Y	0.8789	likely_pathogenic	0.8403	pathogenic	0.221	Stabilizing	0.998	D	0.819	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.