TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29371	88336;88337;88338	chr2:178557043;178557042;178557041	chr2:179421770;179421769;179421768
N2AB	27730	83413;83414;83415	chr2:178557043;178557042;178557041	chr2:179421770;179421769;179421768
N2A	26803	80632;80633;80634	chr2:178557043;178557042;178557041	chr2:179421770;179421769;179421768
N2B	20306	61141;61142;61143	chr2:178557043;178557042;178557041	chr2:179421770;179421769;179421768
Novex-1	20431	61516;61517;61518	chr2:178557043;178557042;178557041	chr2:179421770;179421769;179421768
Novex-2	20498	61717;61718;61719	chr2:178557043;178557042;178557041	chr2:179421770;179421769;179421768
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: Fn3-102
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1505
• 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
I/F	None	None	0.001	N	0.499	0.222	0.499345284858	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85801E-06	0	0
I/N	rs767890385	-2.083	0.484	N	0.699	0.311	0.72990446813	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/N	rs767890385	-2.083	0.484	N	0.699	0.311	0.72990446813	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/N	rs767890385	-2.083	0.484	N	0.699	0.311	0.72990446813	gnomAD-4.0.0	1.85912E-06	None	None	None	None	N	None	2.66937E-05	0	None	0	0	None	0	0	8.47571E-07	0	0
I/T	rs767890385	-2.296	0.117	N	0.665	0.183	None	gnomAD-2.1.1	4.02E-05	None	None	None	None	N	None	6.46E-05	1.73974E-04	None	0	5.61E-05	None	3.27E-05	None	0	8.89E-06	0
I/T	rs767890385	-2.296	0.117	N	0.665	0.183	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs767890385	-2.296	0.117	N	0.665	0.183	None	gnomAD-4.0.0	2.5408E-05	None	None	None	None	N	None	2.66937E-05	1.16706E-04	None	0	0	None	0	0	2.62747E-05	1.09798E-05	0
I/V	rs1229603276	-1.081	None	N	0.259	0.073	0.313210971179	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs1229603276	-1.081	None	N	0.259	0.073	0.313210971179	gnomAD-4.0.0	3.18286E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	2.85801E-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
I/A	0.268	likely_benign	0.2126	benign	-2.59	Highly Destabilizing	0.035	N	0.635	neutral	None	None	None	None	N
I/C	0.6379	likely_pathogenic	0.5696	pathogenic	-1.801	Destabilizing	0.935	D	0.663	neutral	None	None	None	None	N
I/D	0.725	likely_pathogenic	0.6686	pathogenic	-2.893	Highly Destabilizing	0.555	D	0.689	prob.neutral	None	None	None	None	N
I/E	0.6427	likely_pathogenic	0.584	pathogenic	-2.658	Highly Destabilizing	0.555	D	0.683	prob.neutral	None	None	None	None	N
I/F	0.1508	likely_benign	0.1239	benign	-1.515	Destabilizing	0.001	N	0.499	neutral	N	0.48229379	None	None	N
I/G	0.6983	likely_pathogenic	0.6155	pathogenic	-3.133	Highly Destabilizing	0.38	N	0.684	prob.neutral	None	None	None	None	N
I/H	0.4531	ambiguous	0.386	ambiguous	-2.583	Highly Destabilizing	0.935	D	0.689	prob.neutral	None	None	None	None	N
I/K	0.5368	ambiguous	0.4764	ambiguous	-2.021	Highly Destabilizing	0.38	N	0.673	neutral	None	None	None	None	N
I/L	0.0955	likely_benign	0.0941	benign	-1.015	Destabilizing	None	N	0.279	neutral	N	0.490369481	None	None	N
I/M	0.0756	likely_benign	0.0806	benign	-0.991	Destabilizing	0.004	N	0.509	neutral	N	0.49984184	None	None	N
I/N	0.2981	likely_benign	0.2404	benign	-2.38	Highly Destabilizing	0.484	N	0.699	prob.neutral	N	0.473606829	None	None	N
I/P	0.9711	likely_pathogenic	0.9629	pathogenic	-1.522	Destabilizing	0.791	D	0.7	prob.neutral	None	None	None	None	N
I/Q	0.4535	ambiguous	0.4176	ambiguous	-2.227	Highly Destabilizing	0.38	N	0.691	prob.neutral	None	None	None	None	N
I/R	0.4104	ambiguous	0.3309	benign	-1.733	Destabilizing	0.38	N	0.699	prob.neutral	None	None	None	None	N
I/S	0.2445	likely_benign	0.1986	benign	-3.056	Highly Destabilizing	0.317	N	0.65	neutral	N	0.480568589	None	None	N
I/T	0.1205	likely_benign	0.1011	benign	-2.681	Highly Destabilizing	0.117	N	0.665	neutral	N	0.5002584	None	None	N
I/V	0.0701	likely_benign	0.0655	benign	-1.522	Destabilizing	None	N	0.259	neutral	N	0.467281977	None	None	N
I/W	0.7057	likely_pathogenic	0.6686	pathogenic	-1.92	Destabilizing	0.935	D	0.698	prob.neutral	None	None	None	None	N
I/Y	0.4685	ambiguous	0.4125	ambiguous	-1.638	Destabilizing	0.235	N	0.694	prob.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.