TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25925	77998;77999;78000	chr2:178568359;178568358;178568357	chr2:179433086;179433085;179433084
N2AB	24284	73075;73076;73077	chr2:178568359;178568358;178568357	chr2:179433086;179433085;179433084
N2A	23357	70294;70295;70296	chr2:178568359;178568358;178568357	chr2:179433086;179433085;179433084
N2B	16860	50803;50804;50805	chr2:178568359;178568358;178568357	chr2:179433086;179433085;179433084
Novex-1	16985	51178;51179;51180	chr2:178568359;178568358;178568357	chr2:179433086;179433085;179433084
Novex-2	17052	51379;51380;51381	chr2:178568359;178568358;178568357	chr2:179433086;179433085;179433084
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: Fn3-76
• Domain position: 36
• Structural Position: 37
• Q(SASA): 0.1401
• 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/T	rs1048567784	-0.812	0.999	N	0.589	0.524	0.378847511475	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
N/T	rs1048567784	-0.812	0.999	N	0.589	0.524	0.378847511475	gnomAD-4.0.0	3.18464E-06	None	None	None	None	N	None	0	2.28843E-05	None	0	0	None	0	0	2.85976E-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	0.7618	likely_pathogenic	0.8158	pathogenic	-1.046	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
N/C	0.5978	likely_pathogenic	0.6203	pathogenic	-0.361	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
N/D	0.7982	likely_pathogenic	0.8662	pathogenic	-1.365	Destabilizing	0.999	D	0.55	neutral	N	0.48075008	None	None	N
N/E	0.9769	likely_pathogenic	0.9855	pathogenic	-1.211	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
N/F	0.9763	likely_pathogenic	0.9864	pathogenic	-0.732	Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
N/G	0.5218	ambiguous	0.5808	pathogenic	-1.412	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	N
N/H	0.399	ambiguous	0.4822	ambiguous	-1.018	Destabilizing	1.0	D	0.671	neutral	N	0.496066089	None	None	N
N/I	0.9729	likely_pathogenic	0.9827	pathogenic	-0.094	Destabilizing	1.0	D	0.923	deleterious	N	0.499868293	None	None	N
N/K	0.9434	likely_pathogenic	0.9682	pathogenic	-0.318	Destabilizing	1.0	D	0.648	neutral	N	0.467365859	None	None	N
N/L	0.9224	likely_pathogenic	0.9428	pathogenic	-0.094	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
N/M	0.9511	likely_pathogenic	0.967	pathogenic	0.327	Stabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
N/P	0.9943	likely_pathogenic	0.9958	pathogenic	-0.382	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
N/Q	0.9029	likely_pathogenic	0.9341	pathogenic	-1.087	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
N/R	0.8994	likely_pathogenic	0.9314	pathogenic	-0.331	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
N/S	0.1674	likely_benign	0.1908	benign	-1.163	Destabilizing	0.999	D	0.521	neutral	N	0.480403203	None	None	N
N/T	0.7499	likely_pathogenic	0.8108	pathogenic	-0.816	Destabilizing	0.999	D	0.589	neutral	N	0.472925721	None	None	N
N/V	0.9467	likely_pathogenic	0.9608	pathogenic	-0.382	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
N/W	0.9896	likely_pathogenic	0.9933	pathogenic	-0.496	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
N/Y	0.7509	likely_pathogenic	0.8293	pathogenic	-0.229	Destabilizing	1.0	D	0.91	deleterious	N	0.468330591	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.