TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18921	56986;56987;56988	chr2:178598949;178598948;178598947	chr2:179463676;179463675;179463674
N2AB	17280	52063;52064;52065	chr2:178598949;178598948;178598947	chr2:179463676;179463675;179463674
N2A	16353	49282;49283;49284	chr2:178598949;178598948;178598947	chr2:179463676;179463675;179463674
N2B	9856	29791;29792;29793	chr2:178598949;178598948;178598947	chr2:179463676;179463675;179463674
Novex-1	9981	30166;30167;30168	chr2:178598949;178598948;178598947	chr2:179463676;179463675;179463674
Novex-2	10048	30367;30368;30369	chr2:178598949;178598948;178598947	chr2:179463676;179463675;179463674
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-25
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0786
• 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
L/P	rs2052542764	None	0.999	N	0.83	0.674	0.798510955838	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs2052542764	None	0.999	N	0.83	0.674	0.798510955838	gnomAD-4.0.0	3.0454E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61505E-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
L/A	0.9596	likely_pathogenic	0.9556	pathogenic	-2.853	Highly Destabilizing	0.992	D	0.574	neutral	None	None	None	None	N
L/C	0.9474	likely_pathogenic	0.9519	pathogenic	-1.943	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9998	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/E	0.9985	likely_pathogenic	0.9978	pathogenic	-3.162	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/F	0.9702	likely_pathogenic	0.9739	pathogenic	-1.803	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
L/G	0.9969	likely_pathogenic	0.996	pathogenic	-3.366	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/H	0.9988	likely_pathogenic	0.9983	pathogenic	-3.035	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
L/I	0.1742	likely_benign	0.1948	benign	-1.275	Destabilizing	0.611	D	0.247	neutral	None	None	None	None	N
L/K	0.9981	likely_pathogenic	0.997	pathogenic	-2.374	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/M	0.509	ambiguous	0.5591	ambiguous	-1.476	Destabilizing	0.998	D	0.595	neutral	N	0.472844177	None	None	N
L/N	0.9991	likely_pathogenic	0.9987	pathogenic	-3.132	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/P	0.9983	likely_pathogenic	0.998	pathogenic	-1.799	Destabilizing	0.999	D	0.83	deleterious	N	0.50133046	None	None	N
L/Q	0.9967	likely_pathogenic	0.9951	pathogenic	-2.758	Highly Destabilizing	0.999	D	0.82	deleterious	N	0.512851349	None	None	N
L/R	0.9962	likely_pathogenic	0.9945	pathogenic	-2.475	Highly Destabilizing	0.999	D	0.817	deleterious	N	0.512851349	None	None	N
L/S	0.9983	likely_pathogenic	0.9979	pathogenic	-3.491	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
L/T	0.9745	likely_pathogenic	0.9688	pathogenic	-3.058	Highly Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
L/V	0.1751	likely_benign	0.1923	benign	-1.799	Destabilizing	0.543	D	0.326	neutral	N	0.391986424	None	None	N
L/W	0.998	likely_pathogenic	0.9979	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/Y	0.9978	likely_pathogenic	0.9975	pathogenic	-1.999	Destabilizing	1.0	D	0.679	prob.neutral	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.