TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17403	52432;52433;52434	chr2:178608804;178608803;178608802	chr2:179473531;179473530;179473529
N2AB	15762	47509;47510;47511	chr2:178608804;178608803;178608802	chr2:179473531;179473530;179473529
N2A	14835	44728;44729;44730	chr2:178608804;178608803;178608802	chr2:179473531;179473530;179473529
N2B	8338	25237;25238;25239	chr2:178608804;178608803;178608802	chr2:179473531;179473530;179473529
Novex-1	8463	25612;25613;25614	chr2:178608804;178608803;178608802	chr2:179473531;179473530;179473529
Novex-2	8530	25813;25814;25815	chr2:178608804;178608803;178608802	chr2:179473531;179473530;179473529
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-14
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1286
• Predicted PPI site: I

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/H	rs778111199	-1.12	1.0	N	0.689	0.536	0.241664281697	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
N/K	None	None	1.0	N	0.687	0.372	0.187945064343	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
N/A	0.7529	likely_pathogenic	0.761	pathogenic	-1.103	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
N/C	0.4282	ambiguous	0.4475	ambiguous	-0.636	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
N/D	0.8362	likely_pathogenic	0.8466	pathogenic	-1.888	Destabilizing	0.999	D	0.573	neutral	N	0.478775071	None	None	I
N/E	0.9742	likely_pathogenic	0.9796	pathogenic	-1.702	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	I
N/F	0.9256	likely_pathogenic	0.9308	pathogenic	-0.822	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
N/G	0.6337	likely_pathogenic	0.6095	pathogenic	-1.453	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	I
N/H	0.4014	ambiguous	0.4014	ambiguous	-0.994	Destabilizing	1.0	D	0.689	prob.neutral	N	0.518422874	None	None	I
N/I	0.9103	likely_pathogenic	0.9225	pathogenic	-0.184	Destabilizing	1.0	D	0.889	deleterious	N	0.491145334	None	None	I
N/K	0.9568	likely_pathogenic	0.9597	pathogenic	-0.316	Destabilizing	1.0	D	0.687	prob.neutral	N	0.514342418	None	None	I
N/L	0.8209	likely_pathogenic	0.8243	pathogenic	-0.184	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
N/M	0.9067	likely_pathogenic	0.9137	pathogenic	0.107	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
N/P	0.9921	likely_pathogenic	0.9935	pathogenic	-0.464	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
N/Q	0.8995	likely_pathogenic	0.9022	pathogenic	-1.134	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
N/R	0.8974	likely_pathogenic	0.9044	pathogenic	-0.311	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
N/S	0.1752	likely_benign	0.1747	benign	-1.237	Destabilizing	0.999	D	0.533	neutral	N	0.505453576	None	None	I
N/T	0.6529	likely_pathogenic	0.6648	pathogenic	-0.874	Destabilizing	0.999	D	0.649	neutral	N	0.475559067	None	None	I
N/V	0.8996	likely_pathogenic	0.9077	pathogenic	-0.464	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
N/W	0.9744	likely_pathogenic	0.9745	pathogenic	-0.664	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
N/Y	0.6247	likely_pathogenic	0.6555	pathogenic	-0.332	Destabilizing	1.0	D	0.878	deleterious	N	0.471293106	None	None	I

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.