TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29262	88009;88010;88011	chr2:178557478;178557477;178557476	chr2:179422205;179422204;179422203
N2AB	27621	83086;83087;83088	chr2:178557478;178557477;178557476	chr2:179422205;179422204;179422203
N2A	26694	80305;80306;80307	chr2:178557478;178557477;178557476	chr2:179422205;179422204;179422203
N2B	20197	60814;60815;60816	chr2:178557478;178557477;178557476	chr2:179422205;179422204;179422203
Novex-1	20322	61189;61190;61191	chr2:178557478;178557477;178557476	chr2:179422205;179422204;179422203
Novex-2	20389	61390;61391;61392	chr2:178557478;178557477;178557476	chr2:179422205;179422204;179422203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-101
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.9566
• 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
V/A	rs1053653300	0.033	0.704	N	0.25	0.105	0.353974658523	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.89E-06	0
V/A	rs1053653300	0.033	0.704	N	0.25	0.105	0.353974658523	gnomAD-4.0.0	2.73669E-06	None	None	None	None	I	None	0	2.23594E-05	None	0	5.04236E-05	None	0	0	8.99421E-07	0	0
V/G	rs1053653300	-0.151	0.92	N	0.364	0.22	0.7110473393	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/G	rs1053653300	-0.151	0.92	N	0.364	0.22	0.7110473393	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
V/G	rs1053653300	-0.151	0.92	N	0.364	0.22	0.7110473393	gnomAD-4.0.0	4.95732E-06	None	None	None	None	I	None	8.00747E-05	0	None	0	0	None	0	0	0	1.09791E-05	1.60102E-05
V/L	rs1466272644	0.054	0.906	N	0.366	0.103	0.278143212241	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
V/L	rs1466272644	0.054	0.906	N	0.366	0.103	0.278143212241	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	0	4.58235E-04	0	0	0	None	0	0	0	0	0
V/L	rs1466272644	0.054	0.906	N	0.366	0.103	0.278143212241	gnomAD-4.0.0	5.57685E-06	None	None	None	None	I	None	0	1.5E-04	None	0	0	None	0	0	0	0	0
V/M	None	None	0.996	D	0.337	0.19	0.347438807231	gnomAD-4.0.0	6.84174E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99421E-07	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
V/A	0.2913	likely_benign	0.2863	benign	-0.328	Destabilizing	0.704	D	0.25	neutral	N	0.447482708	None	None	I
V/C	0.8314	likely_pathogenic	0.8402	pathogenic	-0.803	Destabilizing	0.999	D	0.303	neutral	None	None	None	None	I
V/D	0.6986	likely_pathogenic	0.6367	pathogenic	-0.324	Destabilizing	0.939	D	0.388	neutral	None	None	None	None	I
V/E	0.6085	likely_pathogenic	0.5463	ambiguous	-0.443	Destabilizing	0.704	D	0.321	neutral	N	0.472013006	None	None	I
V/F	0.314	likely_benign	0.3075	benign	-0.729	Destabilizing	0.997	D	0.308	neutral	None	None	None	None	I
V/G	0.3644	ambiguous	0.3558	ambiguous	-0.376	Destabilizing	0.92	D	0.364	neutral	N	0.491505631	None	None	I
V/H	0.7854	likely_pathogenic	0.7722	pathogenic	-0.01	Destabilizing	0.991	D	0.267	neutral	None	None	None	None	I
V/I	0.095	likely_benign	0.0943	benign	-0.344	Destabilizing	0.969	D	0.367	neutral	None	None	None	None	I
V/K	0.6461	likely_pathogenic	0.5931	pathogenic	-0.364	Destabilizing	0.079	N	0.17	neutral	None	None	None	None	I
V/L	0.2744	likely_benign	0.2715	benign	-0.344	Destabilizing	0.906	D	0.366	neutral	N	0.484616944	None	None	I
V/M	0.2425	likely_benign	0.2429	benign	-0.572	Destabilizing	0.996	D	0.337	neutral	D	0.524444769	None	None	I
V/N	0.5112	ambiguous	0.4541	ambiguous	-0.166	Destabilizing	0.939	D	0.385	neutral	None	None	None	None	I
V/P	0.5442	ambiguous	0.5489	ambiguous	-0.312	Destabilizing	0.991	D	0.353	neutral	None	None	None	None	I
V/Q	0.551	ambiguous	0.522	ambiguous	-0.378	Destabilizing	0.373	N	0.229	neutral	None	None	None	None	I
V/R	0.5805	likely_pathogenic	0.5471	ambiguous	0.067	Stabilizing	0.884	D	0.381	neutral	None	None	None	None	I
V/S	0.3667	ambiguous	0.343	ambiguous	-0.472	Destabilizing	0.373	N	0.229	neutral	None	None	None	None	I
V/T	0.3719	ambiguous	0.3258	benign	-0.502	Destabilizing	0.759	D	0.299	neutral	None	None	None	None	I
V/W	0.9361	likely_pathogenic	0.9323	pathogenic	-0.78	Destabilizing	0.999	D	0.299	neutral	None	None	None	None	I
V/Y	0.7378	likely_pathogenic	0.7291	pathogenic	-0.509	Destabilizing	0.997	D	0.311	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.