TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29157	87694;87695;87696	chr2:178557885;178557884;178557883	chr2:179422612;179422611;179422610
N2AB	27516	82771;82772;82773	chr2:178557885;178557884;178557883	chr2:179422612;179422611;179422610
N2A	26589	79990;79991;79992	chr2:178557885;178557884;178557883	chr2:179422612;179422611;179422610
N2B	20092	60499;60500;60501	chr2:178557885;178557884;178557883	chr2:179422612;179422611;179422610
Novex-1	20217	60874;60875;60876	chr2:178557885;178557884;178557883	chr2:179422612;179422611;179422610
Novex-2	20284	61075;61076;61077	chr2:178557885;178557884;178557883	chr2:179422612;179422611;179422610
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-100
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.0626
• 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/F	rs1311609495	-1.813	0.999	N	0.753	0.467	0.734502758406	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/F	rs1311609495	-1.813	0.999	N	0.753	0.467	0.734502758406	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8578E-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	0.8578	likely_pathogenic	0.8812	pathogenic	-2.749	Highly Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
L/C	0.7419	likely_pathogenic	0.7688	pathogenic	-1.866	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.505	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
L/E	0.995	likely_pathogenic	0.9952	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/F	0.3335	likely_benign	0.4107	ambiguous	-1.689	Destabilizing	0.999	D	0.753	deleterious	N	0.52187484	None	None	N
L/G	0.9811	likely_pathogenic	0.9842	pathogenic	-3.372	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/H	0.9838	likely_pathogenic	0.9869	pathogenic	-3.129	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.559350797	None	None	N
L/I	0.1044	likely_benign	0.1094	benign	-0.869	Destabilizing	0.992	D	0.615	neutral	N	0.51558293	None	None	N
L/K	0.993	likely_pathogenic	0.9934	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/M	0.1688	likely_benign	0.1871	benign	-0.961	Destabilizing	0.985	D	0.533	neutral	None	None	None	None	N
L/N	0.9958	likely_pathogenic	0.9964	pathogenic	-2.979	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
L/P	0.9932	likely_pathogenic	0.9945	pathogenic	-1.487	Destabilizing	1.0	D	0.927	deleterious	D	0.559350797	None	None	N
L/Q	0.9735	likely_pathogenic	0.9779	pathogenic	-2.589	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
L/R	0.9829	likely_pathogenic	0.9851	pathogenic	-2.307	Highly Destabilizing	0.999	D	0.896	deleterious	D	0.559350797	None	None	N
L/S	0.9812	likely_pathogenic	0.9857	pathogenic	-3.514	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/T	0.9341	likely_pathogenic	0.9452	pathogenic	-3.007	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
L/V	0.1029	likely_benign	0.1133	benign	-1.487	Destabilizing	0.992	D	0.642	neutral	N	0.51684958	None	None	N
L/W	0.9167	likely_pathogenic	0.934	pathogenic	-2.118	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/Y	0.9379	likely_pathogenic	0.9528	pathogenic	-1.884	Destabilizing	1.0	D	0.825	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.