TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20607	62044;62045;62046	chr2:178589906;178589905;178589904	chr2:179454633;179454632;179454631
N2AB	18966	57121;57122;57123	chr2:178589906;178589905;178589904	chr2:179454633;179454632;179454631
N2A	18039	54340;54341;54342	chr2:178589906;178589905;178589904	chr2:179454633;179454632;179454631
N2B	11542	34849;34850;34851	chr2:178589906;178589905;178589904	chr2:179454633;179454632;179454631
Novex-1	11667	35224;35225;35226	chr2:178589906;178589905;178589904	chr2:179454633;179454632;179454631
Novex-2	11734	35425;35426;35427	chr2:178589906;178589905;178589904	chr2:179454633;179454632;179454631
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-37
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1584
• 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
E/D	None	None	0.999	N	0.653	0.308	0.269558022972	gnomAD-4.0.0	2.0532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47866E-05	0
E/K	None	None	0.999	N	0.684	0.436	0.341460817117	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-06	0	0
E/Q	rs1396768636	None	1.0	N	0.752	0.416	0.276065633971	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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
E/A	0.8842	likely_pathogenic	0.8826	pathogenic	-1.737	Destabilizing	0.999	D	0.693	prob.neutral	D	0.524164293	None	None	N
E/C	0.9901	likely_pathogenic	0.988	pathogenic	-0.665	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/D	0.9436	likely_pathogenic	0.9506	pathogenic	-1.653	Destabilizing	0.999	D	0.653	neutral	N	0.490184283	None	None	N
E/F	0.9959	likely_pathogenic	0.9961	pathogenic	-1.517	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/G	0.9487	likely_pathogenic	0.9415	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.754	deleterious	N	0.503061525	None	None	N
E/H	0.9893	likely_pathogenic	0.9886	pathogenic	-1.2	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/I	0.9847	likely_pathogenic	0.985	pathogenic	-0.728	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.9791	likely_pathogenic	0.976	pathogenic	-1.436	Destabilizing	0.999	D	0.684	prob.neutral	N	0.498044641	None	None	N
E/L	0.9867	likely_pathogenic	0.9876	pathogenic	-0.728	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/M	0.9771	likely_pathogenic	0.9772	pathogenic	0.008	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/N	0.9845	likely_pathogenic	0.9868	pathogenic	-1.578	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9998	pathogenic	-1.054	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Q	0.7089	likely_pathogenic	0.729	pathogenic	-1.332	Destabilizing	1.0	D	0.752	deleterious	N	0.516537362	None	None	N
E/R	0.9797	likely_pathogenic	0.9772	pathogenic	-1.266	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/S	0.9307	likely_pathogenic	0.9329	pathogenic	-2.196	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/T	0.9722	likely_pathogenic	0.9726	pathogenic	-1.854	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/V	0.9639	likely_pathogenic	0.9652	pathogenic	-1.054	Destabilizing	1.0	D	0.753	deleterious	N	0.509783022	None	None	N
E/W	0.9989	likely_pathogenic	0.9988	pathogenic	-1.57	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Y	0.9931	likely_pathogenic	0.9926	pathogenic	-1.306	Destabilizing	1.0	D	0.785	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.