TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29282	88069;88070;88071	chr2:178557418;178557417;178557416	chr2:179422145;179422144;179422143
N2AB	27641	83146;83147;83148	chr2:178557418;178557417;178557416	chr2:179422145;179422144;179422143
N2A	26714	80365;80366;80367	chr2:178557418;178557417;178557416	chr2:179422145;179422144;179422143
N2B	20217	60874;60875;60876	chr2:178557418;178557417;178557416	chr2:179422145;179422144;179422143
Novex-1	20342	61249;61250;61251	chr2:178557418;178557417;178557416	chr2:179422145;179422144;179422143
Novex-2	20409	61450;61451;61452	chr2:178557418;178557417;178557416	chr2:179422145;179422144;179422143
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-101
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9944
• Predicted PPI site: I

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
I/V	rs1396385719	-0.119	0.008	N	0.229	0.069	0.338834610459	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	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
I/A	0.8171	likely_pathogenic	0.8789	pathogenic	-0.504	Destabilizing	0.633	D	0.453	neutral	None	None	None	None	I
I/C	0.9308	likely_pathogenic	0.9646	pathogenic	-0.807	Destabilizing	0.996	D	0.457	neutral	None	None	None	None	I
I/D	0.9662	likely_pathogenic	0.9855	pathogenic	-0.156	Destabilizing	0.987	D	0.541	neutral	None	None	None	None	I
I/E	0.9623	likely_pathogenic	0.9797	pathogenic	-0.235	Destabilizing	0.961	D	0.547	neutral	None	None	None	None	I
I/F	0.5014	ambiguous	0.5798	pathogenic	-0.614	Destabilizing	0.901	D	0.369	neutral	N	0.503614049	None	None	I
I/G	0.9513	likely_pathogenic	0.9762	pathogenic	-0.611	Destabilizing	0.961	D	0.551	neutral	None	None	None	None	I
I/H	0.907	likely_pathogenic	0.951	pathogenic	0.099	Stabilizing	0.996	D	0.595	neutral	None	None	None	None	I
I/K	0.9002	likely_pathogenic	0.9384	pathogenic	-0.333	Destabilizing	0.961	D	0.551	neutral	None	None	None	None	I
I/L	0.1548	likely_benign	0.1679	benign	-0.335	Destabilizing	0.003	N	0.201	neutral	N	0.472226437	None	None	I
I/M	0.2833	likely_benign	0.3321	benign	-0.647	Destabilizing	0.901	D	0.379	neutral	D	0.522135182	None	None	I
I/N	0.7946	likely_pathogenic	0.8938	pathogenic	-0.228	Destabilizing	0.983	D	0.551	neutral	N	0.486019667	None	None	I
I/P	0.8841	likely_pathogenic	0.9244	pathogenic	-0.364	Destabilizing	0.987	D	0.551	neutral	None	None	None	None	I
I/Q	0.9103	likely_pathogenic	0.9465	pathogenic	-0.378	Destabilizing	0.987	D	0.543	neutral	None	None	None	None	I
I/R	0.8378	likely_pathogenic	0.8906	pathogenic	0.115	Stabilizing	0.961	D	0.553	neutral	None	None	None	None	I
I/S	0.783	likely_pathogenic	0.8798	pathogenic	-0.634	Destabilizing	0.901	D	0.462	neutral	N	0.482037999	None	None	I
I/T	0.8434	likely_pathogenic	0.9037	pathogenic	-0.611	Destabilizing	0.722	D	0.384	neutral	N	0.500085042	None	None	I
I/V	0.1752	likely_benign	0.2088	benign	-0.364	Destabilizing	0.008	N	0.229	neutral	N	0.508589882	None	None	I
I/W	0.9453	likely_pathogenic	0.9665	pathogenic	-0.628	Destabilizing	0.996	D	0.648	neutral	None	None	None	None	I
I/Y	0.833	likely_pathogenic	0.8882	pathogenic	-0.403	Destabilizing	0.961	D	0.391	neutral	None	None	None	None	I

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.