TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16168	48727;48728;48729	chr2:178615443;178615442;178615441	chr2:179480170;179480169;179480168
N2AB	14527	43804;43805;43806	chr2:178615443;178615442;178615441	chr2:179480170;179480169;179480168
N2A	13600	41023;41024;41025	chr2:178615443;178615442;178615441	chr2:179480170;179480169;179480168
N2B	7103	21532;21533;21534	chr2:178615443;178615442;178615441	chr2:179480170;179480169;179480168
Novex-1	7228	21907;21908;21909	chr2:178615443;178615442;178615441	chr2:179480170;179480169;179480168
Novex-2	7295	22108;22109;22110	chr2:178615443;178615442;178615441	chr2:179480170;179480169;179480168
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: Fn3-5
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.1859
• 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/P	rs375878254	-0.412	0.984	D	0.495	0.536	0.368743488249	gnomAD-4.0.0	2.55139E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.0761E-04	2.42248E-04	2.86438E-06	0	9.09863E-05
T/R	None	None	0.968	N	0.519	0.357	0.431035450679	gnomAD-4.0.0	1.59456E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86453E-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
T/A	0.2672	likely_benign	0.3663	ambiguous	-0.765	Destabilizing	0.64	D	0.458	neutral	D	0.545514098	None	None	N
T/C	0.649	likely_pathogenic	0.7792	pathogenic	-0.726	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
T/D	0.5336	ambiguous	0.6131	pathogenic	-1.203	Destabilizing	0.919	D	0.51	neutral	None	None	None	None	N
T/E	0.6746	likely_pathogenic	0.7527	pathogenic	-1.201	Destabilizing	0.919	D	0.513	neutral	None	None	None	None	N
T/F	0.7626	likely_pathogenic	0.8442	pathogenic	-1.134	Destabilizing	0.996	D	0.586	neutral	None	None	None	None	N
T/G	0.2963	likely_benign	0.4003	ambiguous	-0.982	Destabilizing	0.851	D	0.499	neutral	None	None	None	None	N
T/H	0.4184	ambiguous	0.4982	ambiguous	-1.396	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
T/I	0.8398	likely_pathogenic	0.8946	pathogenic	-0.281	Destabilizing	0.984	D	0.505	neutral	D	0.619368542	None	None	N
T/K	0.2997	likely_benign	0.3505	ambiguous	-0.735	Destabilizing	0.896	D	0.509	neutral	N	0.474096046	None	None	N
T/L	0.4377	ambiguous	0.5353	ambiguous	-0.281	Destabilizing	0.919	D	0.497	neutral	None	None	None	None	N
T/M	0.3122	likely_benign	0.383	ambiguous	0.173	Stabilizing	0.999	D	0.521	neutral	None	None	None	None	N
T/N	0.1801	likely_benign	0.208	benign	-0.909	Destabilizing	0.919	D	0.475	neutral	None	None	None	None	N
T/P	0.8087	likely_pathogenic	0.8328	pathogenic	-0.413	Destabilizing	0.984	D	0.495	neutral	D	0.658312772	None	None	N
T/Q	0.4042	ambiguous	0.4991	ambiguous	-1.206	Destabilizing	0.988	D	0.525	neutral	None	None	None	None	N
T/R	0.3323	likely_benign	0.4032	ambiguous	-0.427	Destabilizing	0.968	D	0.519	neutral	N	0.474315199	None	None	N
T/S	0.1072	likely_benign	0.1383	benign	-1.039	Destabilizing	0.046	N	0.157	neutral	N	0.462214267	None	None	N
T/V	0.648	likely_pathogenic	0.7326	pathogenic	-0.413	Destabilizing	0.919	D	0.471	neutral	None	None	None	None	N
T/W	0.9133	likely_pathogenic	0.9501	pathogenic	-1.121	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
T/Y	0.6729	likely_pathogenic	0.7743	pathogenic	-0.797	Destabilizing	0.996	D	0.592	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.