TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16065	48418;48419;48420	chr2:178616598;178616597;178616596	chr2:179481325;179481324;179481323
N2AB	14424	43495;43496;43497	chr2:178616598;178616597;178616596	chr2:179481325;179481324;179481323
N2A	13497	40714;40715;40716	chr2:178616598;178616597;178616596	chr2:179481325;179481324;179481323
N2B	7000	21223;21224;21225	chr2:178616598;178616597;178616596	chr2:179481325;179481324;179481323
Novex-1	7125	21598;21599;21600	chr2:178616598;178616597;178616596	chr2:179481325;179481324;179481323
Novex-2	7192	21799;21800;21801	chr2:178616598;178616597;178616596	chr2:179481325;179481324;179481323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-4
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4682
• 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
G/D	rs1490446261	-0.427	None	N	0.257	0.048	0.0297737177859	gnomAD-4.0.0	6.00162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
G/A	0.0804	likely_benign	0.0809	benign	-0.489	Destabilizing	None	N	0.061	neutral	N	0.417374205	None	None	N
G/C	0.107	likely_benign	0.106	benign	-0.731	Destabilizing	0.295	N	0.413	neutral	N	0.473589396	None	None	N
G/D	0.205	likely_benign	0.2012	benign	-0.975	Destabilizing	None	N	0.257	neutral	N	0.44478098	None	None	N
G/E	0.1729	likely_benign	0.1728	benign	-1.072	Destabilizing	0.016	N	0.447	neutral	None	None	None	None	N
G/F	0.3297	likely_benign	0.3686	ambiguous	-0.961	Destabilizing	0.214	N	0.497	neutral	None	None	None	None	N
G/H	0.2135	likely_benign	0.2331	benign	-1.063	Destabilizing	0.356	N	0.403	neutral	None	None	None	None	N
G/I	0.1265	likely_benign	0.1322	benign	-0.29	Destabilizing	0.038	N	0.472	neutral	None	None	None	None	N
G/K	0.2569	likely_benign	0.2739	benign	-1.185	Destabilizing	0.038	N	0.419	neutral	None	None	None	None	N
G/L	0.1765	likely_benign	0.1983	benign	-0.29	Destabilizing	None	N	0.321	neutral	None	None	None	None	N
G/M	0.2098	likely_benign	0.2316	benign	-0.29	Destabilizing	0.214	N	0.444	neutral	None	None	None	None	N
G/N	0.171	likely_benign	0.1868	benign	-0.751	Destabilizing	0.038	N	0.281	neutral	None	None	None	None	N
G/P	0.7516	likely_pathogenic	0.7815	pathogenic	-0.317	Destabilizing	0.072	N	0.466	neutral	None	None	None	None	N
G/Q	0.1937	likely_benign	0.2032	benign	-0.965	Destabilizing	0.214	N	0.495	neutral	None	None	None	None	N
G/R	0.1862	likely_benign	0.1877	benign	-0.802	Destabilizing	0.055	N	0.471	neutral	N	0.459962771	None	None	N
G/S	0.0728	likely_benign	0.0717	benign	-0.913	Destabilizing	None	N	0.083	neutral	N	0.353381643	None	None	N
G/T	0.0733	likely_benign	0.0771	benign	-0.937	Destabilizing	None	N	0.246	neutral	None	None	None	None	N
G/V	0.0974	likely_benign	0.0995	benign	-0.317	Destabilizing	0.012	N	0.415	neutral	N	0.404613997	None	None	N
G/W	0.2784	likely_benign	0.2913	benign	-1.279	Destabilizing	0.864	D	0.419	neutral	None	None	None	None	N
G/Y	0.2732	likely_benign	0.293	benign	-0.88	Destabilizing	0.356	N	0.467	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.