TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17263	52012;52013;52014	chr2:178609523;178609522;178609521	chr2:179474250;179474249;179474248
N2AB	15622	47089;47090;47091	chr2:178609523;178609522;178609521	chr2:179474250;179474249;179474248
N2A	14695	44308;44309;44310	chr2:178609523;178609522;178609521	chr2:179474250;179474249;179474248
N2B	8198	24817;24818;24819	chr2:178609523;178609522;178609521	chr2:179474250;179474249;179474248
Novex-1	8323	25192;25193;25194	chr2:178609523;178609522;178609521	chr2:179474250;179474249;179474248
Novex-2	8390	25393;25394;25395	chr2:178609523;178609522;178609521	chr2:179474250;179474249;179474248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-112
• Domain position: 13
• Structural Position: 25
• Q(SASA): 0.3032
• 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
D/E	rs768268605	None	None	N	0.141	0.033	0.0716867268079	gnomAD-4.0.0	6.84725E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99975E-07	0	0
D/H	None	None	0.427	N	0.421	0.083	0.170165803431	gnomAD-4.0.0	9.60257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05E-05	0	0
D/N	None	None	0.001	N	0.325	0.078	0.136095386433	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.157	likely_benign	0.1562	benign	-0.424	Destabilizing	0.042	N	0.372	neutral	N	0.461001005	None	None	N
D/C	0.4921	ambiguous	0.5038	ambiguous	0.073	Stabilizing	0.002	N	0.357	neutral	None	None	None	None	N
D/E	0.1213	likely_benign	0.1218	benign	-0.424	Destabilizing	None	N	0.141	neutral	N	0.361930089	None	None	N
D/F	0.5217	ambiguous	0.5388	ambiguous	-0.46	Destabilizing	0.331	N	0.479	neutral	None	None	None	None	N
D/G	0.2165	likely_benign	0.2032	benign	-0.628	Destabilizing	None	N	0.19	neutral	N	0.456997908	None	None	N
D/H	0.2589	likely_benign	0.2678	benign	-0.484	Destabilizing	0.427	N	0.421	neutral	N	0.491150554	None	None	N
D/I	0.3786	ambiguous	0.3858	ambiguous	0.067	Stabilizing	0.667	D	0.505	neutral	None	None	None	None	N
D/K	0.3174	likely_benign	0.3013	benign	0.237	Stabilizing	0.124	N	0.399	neutral	None	None	None	None	N
D/L	0.3898	ambiguous	0.392	ambiguous	0.067	Stabilizing	0.22	N	0.442	neutral	None	None	None	None	N
D/M	0.4728	ambiguous	0.4874	ambiguous	0.359	Stabilizing	0.859	D	0.449	neutral	None	None	None	None	N
D/N	0.1079	likely_benign	0.1096	benign	-0.045	Destabilizing	0.001	N	0.325	neutral	N	0.430216738	None	None	N
D/P	0.9542	likely_pathogenic	0.9389	pathogenic	-0.075	Destabilizing	0.667	D	0.463	neutral	None	None	None	None	N
D/Q	0.2319	likely_benign	0.2281	benign	-0.027	Destabilizing	0.124	N	0.375	neutral	None	None	None	None	N
D/R	0.3804	ambiguous	0.363	ambiguous	0.301	Stabilizing	0.22	N	0.485	neutral	None	None	None	None	N
D/S	0.115	likely_benign	0.1143	benign	-0.154	Destabilizing	0.002	N	0.157	neutral	None	None	None	None	N
D/T	0.1972	likely_benign	0.1952	benign	0.004	Stabilizing	0.124	N	0.409	neutral	None	None	None	None	N
D/V	0.2203	likely_benign	0.2199	benign	-0.075	Destabilizing	0.175	N	0.435	neutral	N	0.457088147	None	None	N
D/W	0.8357	likely_pathogenic	0.8381	pathogenic	-0.338	Destabilizing	0.958	D	0.453	neutral	None	None	None	None	N
D/Y	0.2086	likely_benign	0.2196	benign	-0.23	Destabilizing	0.007	N	0.313	neutral	N	0.454325749	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.