TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29204	87835;87836;87837	chr2:178557744;178557743;178557742	chr2:179422471;179422470;179422469
N2AB	27563	82912;82913;82914	chr2:178557744;178557743;178557742	chr2:179422471;179422470;179422469
N2A	26636	80131;80132;80133	chr2:178557744;178557743;178557742	chr2:179422471;179422470;179422469
N2B	20139	60640;60641;60642	chr2:178557744;178557743;178557742	chr2:179422471;179422470;179422469
Novex-1	20264	61015;61016;61017	chr2:178557744;178557743;178557742	chr2:179422471;179422470;179422469
Novex-2	20331	61216;61217;61218	chr2:178557744;178557743;178557742	chr2:179422471;179422470;179422469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-100
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4124
• 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
T/A	None	None	0.477	N	0.427	0.188	0.21737058555	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/I	rs72648228	-0.316	0.928	N	0.45	0.274	0.309530620856	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
T/I	rs72648228	-0.316	0.928	N	0.45	0.274	0.309530620856	gnomAD-4.0.0	6.84163E-07	None	None	None	None	N	None	0	0	None	0	2.51889E-05	None	0	0	0	0	0
T/K	None	None	0.006	N	0.267	0.146	0.213573922156	gnomAD-4.0.0	6.84163E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99421E-07	0	0
T/P	rs765145227	-0.444	0.928	N	0.449	0.298	0.20549828249	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
T/P	rs765145227	-0.444	0.928	N	0.449	0.298	0.20549828249	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/P	rs765145227	-0.444	0.928	N	0.449	0.298	0.20549828249	gnomAD-4.0.0	6.56883E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46981E-05	0	0
T/R	rs72648228	-0.301	0.761	N	0.427	0.104	None	gnomAD-2.1.1	1.96155E-04	None	None	None	None	N	None	2.23141E-03	2.83E-05	None	0	0	None	0	None	0	0	0
T/R	rs72648228	-0.301	0.761	N	0.427	0.104	None	gnomAD-3.1.2	5.12517E-04	None	None	None	None	N	None	1.7852E-03	1.96309E-04	0	0	0	None	0	0	0	0	4.78469E-04
T/R	rs72648228	-0.301	0.761	N	0.427	0.104	None	1000 genomes	1.39776E-03	None	None	None	None	N	None	5.3E-03	0	None	None	0	0	None	None	None	0	None
T/R	rs72648228	-0.301	0.761	N	0.427	0.104	None	gnomAD-4.0.0	1.05951E-04	None	None	None	None	N	None	2.0785E-03	9.99633E-05	None	0	0	None	0	0	0	0	1.44041E-04

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
T/A	0.0636	likely_benign	0.0675	benign	-0.554	Destabilizing	0.477	N	0.427	neutral	N	0.463297523	None	None	N
T/C	0.2958	likely_benign	0.3281	benign	-0.372	Destabilizing	0.995	D	0.477	neutral	None	None	None	None	N
T/D	0.4568	ambiguous	0.5079	ambiguous	-0.131	Destabilizing	0.894	D	0.431	neutral	None	None	None	None	N
T/E	0.2815	likely_benign	0.2759	benign	-0.186	Destabilizing	0.547	D	0.461	neutral	None	None	None	None	N
T/F	0.2785	likely_benign	0.3357	benign	-0.817	Destabilizing	0.981	D	0.571	neutral	None	None	None	None	N
T/G	0.2171	likely_benign	0.2517	benign	-0.74	Destabilizing	0.707	D	0.49	neutral	None	None	None	None	N
T/H	0.2225	likely_benign	0.2665	benign	-1.02	Destabilizing	0.985	D	0.562	neutral	None	None	None	None	N
T/I	0.147	likely_benign	0.1776	benign	-0.171	Destabilizing	0.928	D	0.45	neutral	N	0.516172002	None	None	N
T/K	0.1148	likely_benign	0.1098	benign	-0.612	Destabilizing	0.006	N	0.267	neutral	N	0.479576484	None	None	N
T/L	0.0837	likely_benign	0.0969	benign	-0.171	Destabilizing	0.707	D	0.467	neutral	None	None	None	None	N
T/M	0.082	likely_benign	0.0929	benign	0.097	Stabilizing	0.995	D	0.455	neutral	None	None	None	None	N
T/N	0.1366	likely_benign	0.1659	benign	-0.41	Destabilizing	0.894	D	0.507	neutral	None	None	None	None	N
T/P	0.0817	likely_benign	0.095	benign	-0.268	Destabilizing	0.928	D	0.449	neutral	N	0.388017825	None	None	N
T/Q	0.1647	likely_benign	0.1687	benign	-0.679	Destabilizing	0.809	D	0.45	neutral	None	None	None	None	N
T/R	0.1052	likely_benign	0.093	benign	-0.269	Destabilizing	0.761	D	0.427	neutral	N	0.494545936	None	None	N
T/S	0.1119	likely_benign	0.1309	benign	-0.646	Destabilizing	0.477	N	0.454	neutral	N	0.476517536	None	None	N
T/V	0.1051	likely_benign	0.1208	benign	-0.268	Destabilizing	0.707	D	0.499	neutral	None	None	None	None	N
T/W	0.6016	likely_pathogenic	0.6265	pathogenic	-0.753	Destabilizing	0.995	D	0.611	neutral	None	None	None	None	N
T/Y	0.3077	likely_benign	0.3418	ambiguous	-0.521	Destabilizing	0.981	D	0.573	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.