TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6795	20608;20609;20610	chr2:178725939;178725938;178725937	chr2:179590666;179590665;179590664
N2AB	6478	19657;19658;19659	chr2:178725939;178725938;178725937	chr2:179590666;179590665;179590664
N2A	5551	16876;16877;16878	chr2:178725939;178725938;178725937	chr2:179590666;179590665;179590664
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-52
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2397
• 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
Y/H	None	None	0.002	N	0.16	0.332	0.326881540566	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
Y/A	0.6361	likely_pathogenic	0.5703	pathogenic	-2.721	Highly Destabilizing	0.129	N	0.483	neutral	None	None	None	None	N
Y/C	0.168	likely_benign	0.1726	benign	-1.077	Destabilizing	0.978	D	0.561	neutral	D	0.535527275	None	None	N
Y/D	0.5715	likely_pathogenic	0.5264	ambiguous	-1.932	Destabilizing	0.351	N	0.595	neutral	N	0.497419434	None	None	N
Y/E	0.663	likely_pathogenic	0.6275	pathogenic	-1.814	Destabilizing	0.418	N	0.536	neutral	None	None	None	None	N
Y/F	0.0695	likely_benign	0.0616	benign	-1.045	Destabilizing	0.001	N	0.171	neutral	N	0.430055393	None	None	N
Y/G	0.5991	likely_pathogenic	0.5457	ambiguous	-3.071	Highly Destabilizing	0.418	N	0.563	neutral	None	None	None	None	N
Y/H	0.1757	likely_benign	0.1659	benign	-1.475	Destabilizing	0.002	N	0.16	neutral	N	0.497667252	None	None	N
Y/I	0.4199	ambiguous	0.3618	ambiguous	-1.613	Destabilizing	0.264	N	0.518	neutral	None	None	None	None	N
Y/K	0.685	likely_pathogenic	0.6628	pathogenic	-1.488	Destabilizing	0.418	N	0.561	neutral	None	None	None	None	N
Y/L	0.4028	ambiguous	0.3749	ambiguous	-1.613	Destabilizing	0.002	N	0.263	neutral	None	None	None	None	N
Y/M	0.4758	ambiguous	0.4414	ambiguous	-1.14	Destabilizing	0.716	D	0.583	neutral	None	None	None	None	N
Y/N	0.2183	likely_benign	0.1926	benign	-1.851	Destabilizing	0.351	N	0.574	neutral	N	0.498811786	None	None	N
Y/P	0.9917	likely_pathogenic	0.9893	pathogenic	-1.986	Destabilizing	0.836	D	0.591	neutral	None	None	None	None	N
Y/Q	0.4434	ambiguous	0.4123	ambiguous	-1.78	Destabilizing	0.716	D	0.603	neutral	None	None	None	None	N
Y/R	0.5554	ambiguous	0.5246	ambiguous	-1.03	Destabilizing	0.716	D	0.593	neutral	None	None	None	None	N
Y/S	0.269	likely_benign	0.2376	benign	-2.321	Highly Destabilizing	0.021	N	0.408	neutral	N	0.499494049	None	None	N
Y/T	0.4416	ambiguous	0.4035	ambiguous	-2.11	Highly Destabilizing	0.264	N	0.551	neutral	None	None	None	None	N
Y/V	0.3315	likely_benign	0.2882	benign	-1.986	Destabilizing	0.264	N	0.513	neutral	None	None	None	None	N
Y/W	0.4356	ambiguous	0.411	ambiguous	-0.528	Destabilizing	0.94	D	0.545	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.