TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31025	93298;93299;93300	chr2:178548553;178548552;178548551	chr2:179413280;179413279;179413278
N2AB	29384	88375;88376;88377	chr2:178548553;178548552;178548551	chr2:179413280;179413279;179413278
N2A	28457	85594;85595;85596	chr2:178548553;178548552;178548551	chr2:179413280;179413279;179413278
N2B	21960	66103;66104;66105	chr2:178548553;178548552;178548551	chr2:179413280;179413279;179413278
Novex-1	22085	66478;66479;66480	chr2:178548553;178548552;178548551	chr2:179413280;179413279;179413278
Novex-2	22152	66679;66680;66681	chr2:178548553;178548552;178548551	chr2:179413280;179413279;179413278
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-114
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2203
• 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
F/L	None	None	0.999	N	0.606	0.463	0.398872588132	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
F/V	None	None	1.0	N	0.786	0.512	0.519728874731	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
F/A	0.6935	likely_pathogenic	0.5492	ambiguous	-2.332	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
F/C	0.3128	likely_benign	0.2162	benign	-1.638	Destabilizing	1.0	D	0.859	deleterious	N	0.481888857	None	None	N
F/D	0.9732	likely_pathogenic	0.933	pathogenic	-1.067	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
F/E	0.9648	likely_pathogenic	0.9216	pathogenic	-0.957	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
F/G	0.8985	likely_pathogenic	0.8089	pathogenic	-2.688	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
F/H	0.8001	likely_pathogenic	0.6916	pathogenic	-0.969	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
F/I	0.237	likely_benign	0.1575	benign	-1.246	Destabilizing	1.0	D	0.749	deleterious	N	0.371275583	None	None	N
F/K	0.957	likely_pathogenic	0.9105	pathogenic	-1.622	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
F/L	0.8393	likely_pathogenic	0.7649	pathogenic	-1.246	Destabilizing	0.999	D	0.606	neutral	N	0.393805726	None	None	N
F/M	0.5472	ambiguous	0.443	ambiguous	-1.105	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
F/N	0.9081	likely_pathogenic	0.8379	pathogenic	-1.738	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
F/P	0.9721	likely_pathogenic	0.9397	pathogenic	-1.604	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
F/Q	0.9064	likely_pathogenic	0.8388	pathogenic	-1.732	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
F/R	0.9045	likely_pathogenic	0.8357	pathogenic	-1.029	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
F/S	0.6895	likely_pathogenic	0.5405	ambiguous	-2.559	Highly Destabilizing	1.0	D	0.864	deleterious	N	0.497434313	None	None	N
F/T	0.7252	likely_pathogenic	0.5908	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
F/V	0.211	likely_benign	0.147	benign	-1.604	Destabilizing	1.0	D	0.786	deleterious	N	0.305663879	None	None	N
F/W	0.6033	likely_pathogenic	0.4788	ambiguous	-0.47	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
F/Y	0.2548	likely_benign	0.1982	benign	-0.77	Destabilizing	0.999	D	0.614	neutral	N	0.476675039	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.