TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24236	72931;72932;72933	chr2:178573426;178573425;178573424	chr2:179438153;179438152;179438151
N2AB	22595	68008;68009;68010	chr2:178573426;178573425;178573424	chr2:179438153;179438152;179438151
N2A	21668	65227;65228;65229	chr2:178573426;178573425;178573424	chr2:179438153;179438152;179438151
N2B	15171	45736;45737;45738	chr2:178573426;178573425;178573424	chr2:179438153;179438152;179438151
Novex-1	15296	46111;46112;46113	chr2:178573426;178573425;178573424	chr2:179438153;179438152;179438151
Novex-2	15363	46312;46313;46314	chr2:178573426;178573425;178573424	chr2:179438153;179438152;179438151
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: Fn3-64
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4379
• 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/I	None	None	0.983	N	0.723	0.461	0.555039636665	gnomAD-4.0.0	3.65921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.74383E-06	0	1.77658E-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	0.6215	likely_pathogenic	0.5865	pathogenic	-0.221	Destabilizing	0.916	D	0.535	neutral	None	None	None	None	N
K/C	0.8573	likely_pathogenic	0.8213	pathogenic	-0.384	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
K/D	0.9332	likely_pathogenic	0.9122	pathogenic	-0.657	Destabilizing	0.845	D	0.529	neutral	None	None	None	None	N
K/E	0.5628	ambiguous	0.5011	ambiguous	-0.648	Destabilizing	0.025	N	0.275	neutral	N	0.50118112	None	None	N
K/F	0.9791	likely_pathogenic	0.9707	pathogenic	-0.606	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
K/G	0.6208	likely_pathogenic	0.5695	pathogenic	-0.454	Destabilizing	0.916	D	0.577	neutral	None	None	None	None	N
K/H	0.6045	likely_pathogenic	0.5702	pathogenic	-0.998	Destabilizing	0.987	D	0.569	neutral	None	None	None	None	N
K/I	0.909	likely_pathogenic	0.881	pathogenic	0.325	Stabilizing	0.983	D	0.723	prob.delet.	N	0.506362754	None	None	N
K/L	0.8561	likely_pathogenic	0.8208	pathogenic	0.325	Stabilizing	0.975	D	0.559	neutral	None	None	None	None	N
K/M	0.6995	likely_pathogenic	0.6442	pathogenic	0.542	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	N
K/N	0.8662	likely_pathogenic	0.821	pathogenic	-0.195	Destabilizing	0.204	N	0.301	neutral	N	0.478824296	None	None	N
K/P	0.9355	likely_pathogenic	0.9285	pathogenic	0.171	Stabilizing	0.987	D	0.577	neutral	None	None	None	None	N
K/Q	0.3097	likely_benign	0.2696	benign	-0.543	Destabilizing	0.935	D	0.521	neutral	N	0.472267384	None	None	N
K/R	0.0809	likely_benign	0.0763	benign	-0.183	Destabilizing	0.892	D	0.481	neutral	N	0.476498893	None	None	N
K/S	0.7354	likely_pathogenic	0.6885	pathogenic	-0.662	Destabilizing	0.916	D	0.477	neutral	None	None	None	None	N
K/T	0.6705	likely_pathogenic	0.6129	pathogenic	-0.504	Destabilizing	0.892	D	0.55	neutral	N	0.484064535	None	None	N
K/V	0.8441	likely_pathogenic	0.7994	pathogenic	0.171	Stabilizing	0.987	D	0.581	neutral	None	None	None	None	N
K/W	0.9482	likely_pathogenic	0.9336	pathogenic	-0.563	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
K/Y	0.9315	likely_pathogenic	0.9166	pathogenic	-0.14	Destabilizing	0.996	D	0.683	prob.neutral	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.