TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18323	55192;55193;55194	chr2:178602435;178602434;178602433	chr2:179467162;179467161;179467160
N2AB	16682	50269;50270;50271	chr2:178602435;178602434;178602433	chr2:179467162;179467161;179467160
N2A	15755	47488;47489;47490	chr2:178602435;178602434;178602433	chr2:179467162;179467161;179467160
N2B	9258	27997;27998;27999	chr2:178602435;178602434;178602433	chr2:179467162;179467161;179467160
Novex-1	9383	28372;28373;28374	chr2:178602435;178602434;178602433	chr2:179467162;179467161;179467160
Novex-2	9450	28573;28574;28575	chr2:178602435;178602434;178602433	chr2:179467162;179467161;179467160
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-21
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1397
• 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
N/K	rs765413044	-0.576	0.998	N	0.593	0.252	0.144782658237	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
N/K	rs765413044	-0.576	0.998	N	0.593	0.252	0.144782658237	gnomAD-4.0.0	4.78123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58698E-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
N/A	0.5482	ambiguous	0.4968	ambiguous	-0.961	Destabilizing	0.997	D	0.59	neutral	None	None	None	None	N
N/C	0.4394	ambiguous	0.421	ambiguous	-0.144	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/D	0.5231	ambiguous	0.5211	ambiguous	-0.671	Destabilizing	0.998	D	0.513	neutral	N	0.507880593	None	None	N
N/E	0.8639	likely_pathogenic	0.8553	pathogenic	-0.524	Destabilizing	0.998	D	0.565	neutral	None	None	None	None	N
N/F	0.876	likely_pathogenic	0.8584	pathogenic	-0.459	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
N/G	0.4951	ambiguous	0.4635	ambiguous	-1.341	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
N/H	0.3717	ambiguous	0.3497	ambiguous	-0.93	Destabilizing	1.0	D	0.719	prob.delet.	N	0.500935978	None	None	N
N/I	0.5719	likely_pathogenic	0.5397	ambiguous	0.03	Stabilizing	0.999	D	0.788	deleterious	D	0.523138047	None	None	N
N/K	0.9199	likely_pathogenic	0.8968	pathogenic	-0.344	Destabilizing	0.998	D	0.593	neutral	N	0.465687254	None	None	N
N/L	0.5253	ambiguous	0.5121	ambiguous	0.03	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
N/M	0.5954	likely_pathogenic	0.5692	pathogenic	0.316	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
N/P	0.8349	likely_pathogenic	0.8251	pathogenic	-0.271	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/Q	0.8117	likely_pathogenic	0.7738	pathogenic	-0.835	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
N/R	0.8941	likely_pathogenic	0.863	pathogenic	-0.47	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
N/S	0.1221	likely_benign	0.1149	benign	-1.048	Destabilizing	0.992	D	0.475	neutral	N	0.479749842	None	None	N
N/T	0.1962	likely_benign	0.1977	benign	-0.705	Destabilizing	0.767	D	0.379	neutral	N	0.473573231	None	None	N
N/V	0.5159	ambiguous	0.5021	ambiguous	-0.271	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
N/W	0.9379	likely_pathogenic	0.9252	pathogenic	-0.198	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
N/Y	0.5789	likely_pathogenic	0.5302	ambiguous	0.014	Stabilizing	1.0	D	0.773	deleterious	N	0.460782866	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.