TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25935	78028;78029;78030	chr2:178568329;178568328;178568327	chr2:179433056;179433055;179433054
N2AB	24294	73105;73106;73107	chr2:178568329;178568328;178568327	chr2:179433056;179433055;179433054
N2A	23367	70324;70325;70326	chr2:178568329;178568328;178568327	chr2:179433056;179433055;179433054
N2B	16870	50833;50834;50835	chr2:178568329;178568328;178568327	chr2:179433056;179433055;179433054
Novex-1	16995	51208;51209;51210	chr2:178568329;178568328;178568327	chr2:179433056;179433055;179433054
Novex-2	17062	51409;51410;51411	chr2:178568329;178568328;178568327	chr2:179433056;179433055;179433054
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-76
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.2936
• 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/S	None	None	0.006	N	0.299	0.128	0.110078149338	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

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	0.1083	likely_benign	0.1333	benign	-0.489	Destabilizing	0.273	N	0.361	neutral	N	0.499741112	None	None	N
T/C	0.5538	ambiguous	0.6213	pathogenic	-0.178	Destabilizing	0.985	D	0.385	neutral	None	None	None	None	N
T/D	0.6458	likely_pathogenic	0.7247	pathogenic	-0.03	Destabilizing	0.894	D	0.326	neutral	None	None	None	None	N
T/E	0.5933	likely_pathogenic	0.6701	pathogenic	-0.118	Destabilizing	0.809	D	0.322	neutral	None	None	None	None	N
T/F	0.6357	likely_pathogenic	0.7376	pathogenic	-1.032	Destabilizing	0.894	D	0.47	neutral	None	None	None	None	N
T/G	0.2272	likely_benign	0.2715	benign	-0.604	Destabilizing	0.547	D	0.375	neutral	None	None	None	None	N
T/H	0.4499	ambiguous	0.5206	ambiguous	-0.987	Destabilizing	0.985	D	0.503	neutral	None	None	None	None	N
T/I	0.6263	likely_pathogenic	0.7279	pathogenic	-0.302	Destabilizing	0.013	N	0.245	neutral	N	0.496767648	None	None	N
T/K	0.3896	ambiguous	0.4189	ambiguous	-0.38	Destabilizing	0.809	D	0.327	neutral	None	None	None	None	N
T/L	0.2304	likely_benign	0.2858	benign	-0.302	Destabilizing	0.293	N	0.327	neutral	None	None	None	None	N
T/M	0.1489	likely_benign	0.1879	benign	0.115	Stabilizing	0.97	D	0.345	neutral	None	None	None	None	N
T/N	0.1792	likely_benign	0.2173	benign	-0.115	Destabilizing	0.761	D	0.31	neutral	N	0.515190567	None	None	N
T/P	0.811	likely_pathogenic	0.8905	pathogenic	-0.338	Destabilizing	0.928	D	0.337	neutral	N	0.475118221	None	None	N
T/Q	0.3581	ambiguous	0.4121	ambiguous	-0.432	Destabilizing	0.894	D	0.325	neutral	None	None	None	None	N
T/R	0.3654	ambiguous	0.4078	ambiguous	-0.072	Destabilizing	0.894	D	0.327	neutral	None	None	None	None	N
T/S	0.0992	likely_benign	0.1145	benign	-0.326	Destabilizing	0.006	N	0.299	neutral	N	0.421240256	None	None	N
T/V	0.3812	ambiguous	0.4525	ambiguous	-0.338	Destabilizing	0.293	N	0.332	neutral	None	None	None	None	N
T/W	0.894	likely_pathogenic	0.9305	pathogenic	-0.997	Destabilizing	0.995	D	0.585	neutral	None	None	None	None	N
T/Y	0.6106	likely_pathogenic	0.7022	pathogenic	-0.728	Destabilizing	0.945	D	0.482	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.