TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6793	20602;20603;20604	chr2:178725945;178725944;178725943	chr2:179590672;179590671;179590670
N2AB	6476	19651;19652;19653	chr2:178725945;178725944;178725943	chr2:179590672;179590671;179590670
N2A	5549	16870;16871;16872	chr2:178725945;178725944;178725943	chr2:179590672;179590671;179590670
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-52
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.1858
• 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/I	rs2079262565	None	None	N	0.205	0.053	0.515490261806	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
V/A	0.1091	likely_benign	0.107	benign	-1.6	Destabilizing	None	N	0.173	neutral	N	0.476126039	None	None	N
V/C	0.6155	likely_pathogenic	0.6337	pathogenic	-0.742	Destabilizing	0.628	D	0.541	neutral	None	None	None	None	N
V/D	0.3449	ambiguous	0.3172	benign	-1.808	Destabilizing	0.072	N	0.548	neutral	None	None	None	None	N
V/E	0.2948	likely_benign	0.2751	benign	-1.751	Destabilizing	0.055	N	0.483	neutral	N	0.465138254	None	None	N
V/F	0.1135	likely_benign	0.1057	benign	-1.136	Destabilizing	0.072	N	0.573	neutral	None	None	None	None	N
V/G	0.1739	likely_benign	0.1612	benign	-1.96	Destabilizing	0.012	N	0.481	neutral	N	0.487187267	None	None	N
V/H	0.3898	ambiguous	0.3734	ambiguous	-1.574	Destabilizing	0.628	D	0.567	neutral	None	None	None	None	N
V/I	0.0639	likely_benign	0.0651	benign	-0.676	Destabilizing	None	N	0.205	neutral	N	0.489634054	None	None	N
V/K	0.3562	ambiguous	0.338	benign	-1.354	Destabilizing	0.072	N	0.484	neutral	None	None	None	None	N
V/L	0.1121	likely_benign	0.1097	benign	-0.676	Destabilizing	None	N	0.209	neutral	N	0.489460696	None	None	N
V/M	0.0904	likely_benign	0.0888	benign	-0.382	Destabilizing	0.214	N	0.522	neutral	None	None	None	None	N
V/N	0.142	likely_benign	0.132	benign	-1.202	Destabilizing	0.072	N	0.551	neutral	None	None	None	None	N
V/P	0.8614	likely_pathogenic	0.8524	pathogenic	-0.953	Destabilizing	0.136	N	0.549	neutral	None	None	None	None	N
V/Q	0.2483	likely_benign	0.2331	benign	-1.316	Destabilizing	0.356	N	0.566	neutral	None	None	None	None	N
V/R	0.3351	likely_benign	0.3155	benign	-0.856	Destabilizing	0.072	N	0.593	neutral	None	None	None	None	N
V/S	0.1042	likely_benign	0.0995	benign	-1.668	Destabilizing	None	N	0.381	neutral	None	None	None	None	N
V/T	0.0864	likely_benign	0.0858	benign	-1.51	Destabilizing	None	N	0.18	neutral	None	None	None	None	N
V/W	0.6915	likely_pathogenic	0.6793	pathogenic	-1.475	Destabilizing	0.864	D	0.591	neutral	None	None	None	None	N
V/Y	0.3909	ambiguous	0.375	ambiguous	-1.146	Destabilizing	0.356	N	0.558	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.