TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16823	50692;50693;50694	chr2:178611842;178611841;178611840	chr2:179476569;179476568;179476567
N2AB	15182	45769;45770;45771	chr2:178611842;178611841;178611840	chr2:179476569;179476568;179476567
N2A	14255	42988;42989;42990	chr2:178611842;178611841;178611840	chr2:179476569;179476568;179476567
N2B	7758	23497;23498;23499	chr2:178611842;178611841;178611840	chr2:179476569;179476568;179476567
Novex-1	7883	23872;23873;23874	chr2:178611842;178611841;178611840	chr2:179476569;179476568;179476567
Novex-2	7950	24073;24074;24075	chr2:178611842;178611841;178611840	chr2:179476569;179476568;179476567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-10
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2278
• 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
Q/K	None	None	0.997	N	0.605	0.363	0.326881540566	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
Q/A	0.4725	ambiguous	0.528	ambiguous	-1.425	Destabilizing	0.997	D	0.597	neutral	None	None	None	None	N
Q/C	0.8433	likely_pathogenic	0.8729	pathogenic	-0.736	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
Q/D	0.9759	likely_pathogenic	0.9747	pathogenic	-2.336	Highly Destabilizing	0.997	D	0.575	neutral	None	None	None	None	N
Q/E	0.2652	likely_benign	0.2493	benign	-1.983	Destabilizing	0.992	D	0.489	neutral	N	0.453360791	None	None	N
Q/F	0.9198	likely_pathogenic	0.9374	pathogenic	-0.741	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
Q/G	0.8088	likely_pathogenic	0.8434	pathogenic	-1.895	Destabilizing	0.997	D	0.657	neutral	None	None	None	None	N
Q/H	0.8142	likely_pathogenic	0.8393	pathogenic	-1.248	Destabilizing	0.999	D	0.726	prob.delet.	N	0.511178063	None	None	N
Q/I	0.6863	likely_pathogenic	0.7162	pathogenic	-0.101	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
Q/K	0.6775	likely_pathogenic	0.6627	pathogenic	-0.619	Destabilizing	0.997	D	0.605	neutral	N	0.478622998	None	None	N
Q/L	0.4262	ambiguous	0.4606	ambiguous	-0.101	Destabilizing	0.997	D	0.657	neutral	N	0.483516158	None	None	N
Q/M	0.4581	ambiguous	0.4987	ambiguous	-0.071	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
Q/N	0.8501	likely_pathogenic	0.8647	pathogenic	-1.607	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
Q/P	0.9867	likely_pathogenic	0.9863	pathogenic	-0.521	Destabilizing	0.999	D	0.723	prob.delet.	D	0.641392302	None	None	N
Q/R	0.6709	likely_pathogenic	0.6724	pathogenic	-0.882	Destabilizing	0.997	D	0.59	neutral	N	0.475096783	None	None	N
Q/S	0.5859	likely_pathogenic	0.6398	pathogenic	-1.886	Destabilizing	0.997	D	0.567	neutral	None	None	None	None	N
Q/T	0.5939	likely_pathogenic	0.6239	pathogenic	-1.35	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
Q/V	0.5562	ambiguous	0.596	pathogenic	-0.521	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
Q/W	0.9647	likely_pathogenic	0.9672	pathogenic	-0.84	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
Q/Y	0.9095	likely_pathogenic	0.9284	pathogenic	-0.442	Destabilizing	0.999	D	0.751	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.