TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29313	88162;88163;88164	chr2:178557325;178557324;178557323	chr2:179422052;179422051;179422050
N2AB	27672	83239;83240;83241	chr2:178557325;178557324;178557323	chr2:179422052;179422051;179422050
N2A	26745	80458;80459;80460	chr2:178557325;178557324;178557323	chr2:179422052;179422051;179422050
N2B	20248	60967;60968;60969	chr2:178557325;178557324;178557323	chr2:179422052;179422051;179422050
Novex-1	20373	61342;61343;61344	chr2:178557325;178557324;178557323	chr2:179422052;179422051;179422050
Novex-2	20440	61543;61544;61545	chr2:178557325;178557324;178557323	chr2:179422052;179422051;179422050
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-101
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.127
• 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
Y/F	None	None	0.211	N	0.653	0.082	0.289098819767	gnomAD-4.0.0	6.84166E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-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
Y/A	0.3037	likely_benign	0.2991	benign	-3.318	Highly Destabilizing	0.001	N	0.479	neutral	None	None	None	None	I
Y/C	0.0824	likely_benign	0.0817	benign	-1.615	Destabilizing	0.001	N	0.529	neutral	N	0.488505398	None	None	I
Y/D	0.6415	likely_pathogenic	0.6411	pathogenic	-3.136	Highly Destabilizing	0.317	N	0.661	neutral	N	0.500082103	None	None	I
Y/E	0.7961	likely_pathogenic	0.7873	pathogenic	-3.018	Highly Destabilizing	0.081	N	0.609	neutral	None	None	None	None	I
Y/F	0.0616	likely_benign	0.0647	benign	-1.401	Destabilizing	0.211	N	0.653	neutral	N	0.471015716	None	None	I
Y/G	0.4154	ambiguous	0.4215	ambiguous	-3.649	Highly Destabilizing	0.081	N	0.633	neutral	None	None	None	None	I
Y/H	0.1919	likely_benign	0.1876	benign	-2.031	Highly Destabilizing	0.484	N	0.651	neutral	N	0.481977848	None	None	I
Y/I	0.3748	ambiguous	0.3667	ambiguous	-2.231	Highly Destabilizing	0.149	N	0.605	neutral	None	None	None	None	I
Y/K	0.7134	likely_pathogenic	0.7053	pathogenic	-2.077	Highly Destabilizing	0.081	N	0.63	neutral	None	None	None	None	I
Y/L	0.3271	likely_benign	0.3154	benign	-2.231	Highly Destabilizing	0.035	N	0.62	neutral	None	None	None	None	I
Y/M	0.3376	likely_benign	0.339	benign	-1.707	Destabilizing	0.791	D	0.614	neutral	None	None	None	None	I
Y/N	0.2487	likely_benign	0.2382	benign	-2.508	Highly Destabilizing	0.317	N	0.646	neutral	N	0.500082103	None	None	I
Y/P	0.9853	likely_pathogenic	0.9851	pathogenic	-2.602	Highly Destabilizing	0.555	D	0.659	neutral	None	None	None	None	I
Y/Q	0.4742	ambiguous	0.4762	ambiguous	-2.468	Highly Destabilizing	0.38	N	0.635	neutral	None	None	None	None	I
Y/R	0.507	ambiguous	0.4968	ambiguous	-1.475	Destabilizing	0.001	N	0.534	neutral	None	None	None	None	I
Y/S	0.1131	likely_benign	0.1132	benign	-2.876	Highly Destabilizing	0.062	N	0.637	neutral	N	0.443194396	None	None	I
Y/T	0.2599	likely_benign	0.2557	benign	-2.672	Highly Destabilizing	0.149	N	0.629	neutral	None	None	None	None	I
Y/V	0.3018	likely_benign	0.2937	benign	-2.602	Highly Destabilizing	0.081	N	0.633	neutral	None	None	None	None	I
Y/W	0.426	ambiguous	0.4129	ambiguous	-0.864	Destabilizing	0.935	D	0.649	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.