TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14921	44986;44987;44988	chr2:178624519;178624518;178624517	chr2:179489246;179489245;179489244
N2AB	13280	40063;40064;40065	chr2:178624519;178624518;178624517	chr2:179489246;179489245;179489244
N2A	12353	37282;37283;37284	chr2:178624519;178624518;178624517	chr2:179489246;179489245;179489244
N2B	5856	17791;17792;17793	chr2:178624519;178624518;178624517	chr2:179489246;179489245;179489244
Novex-1	5981	18166;18167;18168	chr2:178624519;178624518;178624517	chr2:179489246;179489245;179489244
Novex-2	6048	18367;18368;18369	chr2:178624519;178624518;178624517	chr2:179489246;179489245;179489244
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: Ig-100
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.3656
• 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/I	rs776808932	None	0.627	N	0.537	0.287	0.295974979623	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/I	rs776808932	None	0.627	N	0.537	0.287	0.295974979623	gnomAD-4.0.0	2.73851E-06	None	None	None	None	N	None	2.99401E-05	0	None	0	0	None	0	0	8.99909E-07	2.31959E-05	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	0.1264	likely_benign	0.1067	benign	-1.043	Destabilizing	0.001	N	0.207	neutral	N	0.508332558	None	None	N
T/C	0.6727	likely_pathogenic	0.6261	pathogenic	-0.736	Destabilizing	0.944	D	0.511	neutral	None	None	None	None	N
T/D	0.4871	ambiguous	0.4649	ambiguous	-1.027	Destabilizing	0.241	N	0.51	neutral	None	None	None	None	N
T/E	0.3125	likely_benign	0.3311	benign	-0.998	Destabilizing	0.241	N	0.481	neutral	None	None	None	None	N
T/F	0.4543	ambiguous	0.3908	ambiguous	-1.186	Destabilizing	0.818	D	0.578	neutral	None	None	None	None	N
T/G	0.4147	ambiguous	0.3773	ambiguous	-1.321	Destabilizing	0.241	N	0.53	neutral	None	None	None	None	N
T/H	0.3703	ambiguous	0.3774	ambiguous	-1.678	Destabilizing	0.818	D	0.567	neutral	None	None	None	None	N
T/I	0.1868	likely_benign	0.1962	benign	-0.379	Destabilizing	0.627	D	0.537	neutral	N	0.501928201	None	None	N
T/K	0.1573	likely_benign	0.2774	benign	-0.898	Destabilizing	0.001	N	0.292	neutral	N	0.492753553	None	None	N
T/L	0.159	likely_benign	0.1356	benign	-0.379	Destabilizing	0.241	N	0.496	neutral	None	None	None	None	N
T/M	0.1093	likely_benign	0.0934	benign	0.083	Stabilizing	0.981	D	0.506	neutral	None	None	None	None	N
T/N	0.1719	likely_benign	0.1348	benign	-1.047	Destabilizing	0.019	N	0.252	neutral	None	None	None	None	N
T/P	0.1837	likely_benign	0.1801	benign	-0.569	Destabilizing	0.773	D	0.537	neutral	D	0.548472214	None	None	N
T/Q	0.2084	likely_benign	0.2657	benign	-1.23	Destabilizing	0.527	D	0.533	neutral	None	None	None	None	N
T/R	0.1836	likely_benign	0.2377	benign	-0.666	Destabilizing	0.003	N	0.287	neutral	N	0.506813916	None	None	N
T/S	0.2166	likely_benign	0.1667	benign	-1.252	Destabilizing	0.09	N	0.523	neutral	N	0.507714891	None	None	N
T/V	0.1928	likely_benign	0.1772	benign	-0.569	Destabilizing	0.241	N	0.447	neutral	None	None	None	None	N
T/W	0.7052	likely_pathogenic	0.7185	pathogenic	-1.14	Destabilizing	0.981	D	0.606	neutral	None	None	None	None	N
T/Y	0.4302	ambiguous	0.3799	ambiguous	-0.873	Destabilizing	0.818	D	0.578	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.