TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25936	78031;78032;78033	chr2:178568326;178568325;178568324	chr2:179433053;179433052;179433051
N2AB	24295	73108;73109;73110	chr2:178568326;178568325;178568324	chr2:179433053;179433052;179433051
N2A	23368	70327;70328;70329	chr2:178568326;178568325;178568324	chr2:179433053;179433052;179433051
N2B	16871	50836;50837;50838	chr2:178568326;178568325;178568324	chr2:179433053;179433052;179433051
Novex-1	16996	51211;51212;51213	chr2:178568326;178568325;178568324	chr2:179433053;179433052;179433051
Novex-2	17063	51412;51413;51414	chr2:178568326;178568325;178568324	chr2:179433053;179433052;179433051
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: Fn3-76
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.7691
• 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/R	rs533763128	0.214	1.0	N	0.596	0.409	0.636471652698	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93498E-04	None	0	0	0	0	0
T/R	rs533763128	0.214	1.0	N	0.596	0.409	0.636471652698	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
T/R	rs533763128	0.214	1.0	N	0.596	0.409	0.636471652698	gnomAD-4.0.0	6.56996E-06	None	None	None	None	N	None	0	0	None	0	1.93949E-04	None	0	0	0	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	0.1051	likely_benign	0.1209	benign	-0.288	Destabilizing	0.996	D	0.521	neutral	N	0.495623372	None	None	N
T/C	0.7606	likely_pathogenic	0.7846	pathogenic	-0.364	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
T/D	0.7974	likely_pathogenic	0.8365	pathogenic	0.209	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
T/E	0.7197	likely_pathogenic	0.7785	pathogenic	0.134	Stabilizing	1.0	D	0.591	neutral	None	None	None	None	N
T/F	0.6937	likely_pathogenic	0.7782	pathogenic	-0.878	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
T/G	0.4378	ambiguous	0.4891	ambiguous	-0.386	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	N
T/H	0.6564	likely_pathogenic	0.7303	pathogenic	-0.524	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
T/I	0.4403	ambiguous	0.5782	pathogenic	-0.153	Destabilizing	0.992	D	0.557	neutral	N	0.474927183	None	None	N
T/K	0.5703	likely_pathogenic	0.6561	pathogenic	-0.279	Destabilizing	1.0	D	0.599	neutral	N	0.504973574	None	None	N
T/L	0.1964	likely_benign	0.2343	benign	-0.153	Destabilizing	0.994	D	0.532	neutral	None	None	None	None	N
T/M	0.1298	likely_benign	0.1519	benign	-0.199	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
T/N	0.3124	likely_benign	0.3755	ambiguous	-0.107	Destabilizing	1.0	D	0.586	neutral	None	None	None	None	N
T/P	0.2679	likely_benign	0.3423	ambiguous	-0.171	Destabilizing	1.0	D	0.583	neutral	N	0.465012455	None	None	N
T/Q	0.5212	ambiguous	0.5957	pathogenic	-0.285	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
T/R	0.5193	ambiguous	0.6044	pathogenic	0.015	Stabilizing	1.0	D	0.596	neutral	N	0.514998566	None	None	N
T/S	0.2116	likely_benign	0.2448	benign	-0.307	Destabilizing	0.998	D	0.515	neutral	N	0.474632024	None	None	N
T/V	0.2458	likely_benign	0.3133	benign	-0.171	Destabilizing	0.813	D	0.469	neutral	None	None	None	None	N
T/W	0.9278	likely_pathogenic	0.9501	pathogenic	-0.939	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
T/Y	0.7335	likely_pathogenic	0.8029	pathogenic	-0.624	Destabilizing	1.0	D	0.638	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.