TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27090	81493;81494;81495	chr2:178564864;178564863;178564862	chr2:179429591;179429590;179429589
N2AB	25449	76570;76571;76572	chr2:178564864;178564863;178564862	chr2:179429591;179429590;179429589
N2A	24522	73789;73790;73791	chr2:178564864;178564863;178564862	chr2:179429591;179429590;179429589
N2B	18025	54298;54299;54300	chr2:178564864;178564863;178564862	chr2:179429591;179429590;179429589
Novex-1	18150	54673;54674;54675	chr2:178564864;178564863;178564862	chr2:179429591;179429590;179429589
Novex-2	18217	54874;54875;54876	chr2:178564864;178564863;178564862	chr2:179429591;179429590;179429589
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-85
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2318
• 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	rs1230737429	-1.538	0.56	N	0.605	0.293	0.72796072516	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
L/P	rs1230737429	-1.538	0.56	N	0.605	0.293	0.72796072516	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1230737429	-1.538	0.56	N	0.605	0.293	0.72796072516	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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	0.1388	likely_benign	0.128	benign	-2.057	Highly Destabilizing	0.016	N	0.364	neutral	None	None	None	None	N
L/C	0.3453	ambiguous	0.313	benign	-1.42	Destabilizing	0.628	D	0.517	neutral	None	None	None	None	N
L/D	0.4172	ambiguous	0.3945	ambiguous	-1.934	Destabilizing	0.356	N	0.604	neutral	None	None	None	None	N
L/E	0.2322	likely_benign	0.2256	benign	-1.885	Destabilizing	0.136	N	0.571	neutral	None	None	None	None	N
L/F	0.1062	likely_benign	0.0973	benign	-1.395	Destabilizing	0.055	N	0.456	neutral	N	0.497932958	None	None	N
L/G	0.443	ambiguous	0.3933	ambiguous	-2.415	Highly Destabilizing	0.136	N	0.545	neutral	None	None	None	None	N
L/H	0.1614	likely_benign	0.1413	benign	-1.585	Destabilizing	0.828	D	0.588	neutral	N	0.474517381	None	None	N
L/I	0.0569	likely_benign	0.058	benign	-1.108	Destabilizing	None	N	0.237	neutral	N	0.412660845	None	None	N
L/K	0.3114	likely_benign	0.2761	benign	-1.442	Destabilizing	0.072	N	0.52	neutral	None	None	None	None	N
L/M	0.0803	likely_benign	0.0713	benign	-0.984	Destabilizing	0.002	N	0.306	neutral	None	None	None	None	N
L/N	0.1958	likely_benign	0.179	benign	-1.391	Destabilizing	0.356	N	0.603	neutral	None	None	None	None	N
L/P	0.8542	likely_pathogenic	0.8562	pathogenic	-1.397	Destabilizing	0.56	D	0.605	neutral	N	0.498106317	None	None	N
L/Q	0.1424	likely_benign	0.1217	benign	-1.561	Destabilizing	0.356	N	0.572	neutral	None	None	None	None	N
L/R	0.246	likely_benign	0.2169	benign	-0.845	Destabilizing	0.171	N	0.585	neutral	N	0.450024368	None	None	N
L/S	0.1436	likely_benign	0.1249	benign	-2.017	Highly Destabilizing	0.038	N	0.474	neutral	None	None	None	None	N
L/T	0.0813	likely_benign	0.0773	benign	-1.858	Destabilizing	None	N	0.317	neutral	None	None	None	None	N
L/V	0.0606	likely_benign	0.06	benign	-1.397	Destabilizing	None	N	0.262	neutral	N	0.358479644	None	None	N
L/W	0.2188	likely_benign	0.1931	benign	-1.511	Destabilizing	0.864	D	0.595	neutral	None	None	None	None	N
L/Y	0.2471	likely_benign	0.2266	benign	-1.286	Destabilizing	0.356	N	0.549	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.