TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9406	28441;28442;28443	chr2:178710881;178710880;178710879	chr2:179575608;179575607;179575606
N2AB	9089	27490;27491;27492	chr2:178710881;178710880;178710879	chr2:179575608;179575607;179575606
N2A	8162	24709;24710;24711	chr2:178710881;178710880;178710879	chr2:179575608;179575607;179575606
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-80
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3232
• 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
V/M	rs1280284347	-0.286	0.009	None	0.334	0.135	0.31077124679	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/M	rs1280284347	-0.286	0.009	None	0.334	0.135	0.31077124679	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	5.65355E-05	0	None	0	0	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
V/A	0.113	likely_benign	0.1451	benign	-1.45	Destabilizing	None	N	0.154	neutral	None	None	None	None	N
V/C	0.7079	likely_pathogenic	0.7455	pathogenic	-0.896	Destabilizing	0.824	D	0.335	neutral	None	None	None	None	N
V/D	0.3327	likely_benign	0.4346	ambiguous	-1.18	Destabilizing	0.38	N	0.456	neutral	None	None	None	None	N
V/E	0.2119	likely_benign	0.26	benign	-1.16	Destabilizing	0.062	N	0.401	neutral	None	None	None	None	N
V/F	0.1551	likely_benign	0.1671	benign	-1.087	Destabilizing	0.235	N	0.366	neutral	None	None	None	None	N
V/G	0.1699	likely_benign	0.2319	benign	-1.795	Destabilizing	0.062	N	0.439	neutral	None	None	None	None	N
V/H	0.4441	ambiguous	0.5265	ambiguous	-1.394	Destabilizing	0.824	D	0.425	neutral	None	None	None	None	N
V/I	0.0797	likely_benign	0.0827	benign	-0.594	Destabilizing	0.035	N	0.377	neutral	None	None	None	None	N
V/K	0.1831	likely_benign	0.2343	benign	-1.167	Destabilizing	0.081	N	0.404	neutral	None	None	None	None	N
V/L	0.1468	likely_benign	0.1667	benign	-0.594	Destabilizing	None	N	0.084	neutral	None	None	None	None	N
V/M	0.1091	likely_benign	0.1236	benign	-0.446	Destabilizing	0.009	N	0.334	neutral	None	None	None	None	N
V/N	0.2491	likely_benign	0.3249	benign	-0.951	Destabilizing	0.555	D	0.452	neutral	None	None	None	None	N
V/P	0.6872	likely_pathogenic	0.7579	pathogenic	-0.844	Destabilizing	0.555	D	0.417	neutral	None	None	None	None	N
V/Q	0.2056	likely_benign	0.2553	benign	-1.076	Destabilizing	0.016	N	0.355	neutral	None	None	None	None	N
V/R	0.1585	likely_benign	0.1914	benign	-0.723	Destabilizing	0.38	N	0.453	neutral	None	None	None	None	N
V/S	0.1659	likely_benign	0.2145	benign	-1.495	Destabilizing	0.081	N	0.433	neutral	None	None	None	None	N
V/T	0.1127	likely_benign	0.1353	benign	-1.358	Destabilizing	0.149	N	0.297	neutral	None	None	None	None	N
V/W	0.7106	likely_pathogenic	0.7553	pathogenic	-1.318	Destabilizing	0.935	D	0.518	neutral	None	None	None	None	N
V/Y	0.4971	ambiguous	0.5389	ambiguous	-1.003	Destabilizing	0.555	D	0.365	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.