TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24198	72817;72818;72819	chr2:178573540;178573539;178573538	chr2:179438267;179438266;179438265
N2AB	22557	67894;67895;67896	chr2:178573540;178573539;178573538	chr2:179438267;179438266;179438265
N2A	21630	65113;65114;65115	chr2:178573540;178573539;178573538	chr2:179438267;179438266;179438265
N2B	15133	45622;45623;45624	chr2:178573540;178573539;178573538	chr2:179438267;179438266;179438265
Novex-1	15258	45997;45998;45999	chr2:178573540;178573539;178573538	chr2:179438267;179438266;179438265
Novex-2	15325	46198;46199;46200	chr2:178573540;178573539;178573538	chr2:179438267;179438266;179438265
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-63
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.138
• 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
M/T	None	None	0.684	N	0.653	0.39	0.599012661586	gnomAD-4.0.0	1.95311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.37703E-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
M/A	0.4135	ambiguous	0.4699	ambiguous	-2.652	Highly Destabilizing	0.373	N	0.665	neutral	None	None	None	None	N
M/C	0.6398	likely_pathogenic	0.6822	pathogenic	-2.34	Highly Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
M/D	0.9323	likely_pathogenic	0.9441	pathogenic	-2.344	Highly Destabilizing	0.91	D	0.681	prob.neutral	None	None	None	None	N
M/E	0.6583	likely_pathogenic	0.6591	pathogenic	-2.188	Highly Destabilizing	0.59	D	0.631	neutral	None	None	None	None	N
M/F	0.4708	ambiguous	0.526	ambiguous	-1.111	Destabilizing	0.984	D	0.691	prob.neutral	None	None	None	None	N
M/G	0.7374	likely_pathogenic	0.7648	pathogenic	-3.053	Highly Destabilizing	0.742	D	0.644	neutral	None	None	None	None	N
M/H	0.7061	likely_pathogenic	0.7469	pathogenic	-2.434	Highly Destabilizing	0.987	D	0.651	neutral	None	None	None	None	N
M/I	0.5231	ambiguous	0.5598	ambiguous	-1.51	Destabilizing	0.815	D	0.735	prob.delet.	N	0.489753405	None	None	N
M/K	0.4396	ambiguous	0.4573	ambiguous	-1.844	Destabilizing	0.007	N	0.428	neutral	N	0.47372516	None	None	N
M/L	0.2037	likely_benign	0.2055	benign	-1.51	Destabilizing	0.281	N	0.529	neutral	N	0.484462229	None	None	N
M/N	0.6489	likely_pathogenic	0.6965	pathogenic	-1.955	Destabilizing	0.91	D	0.647	neutral	None	None	None	None	N
M/P	0.9936	likely_pathogenic	0.9948	pathogenic	-1.874	Destabilizing	0.953	D	0.643	neutral	None	None	None	None	N
M/Q	0.3591	ambiguous	0.3633	ambiguous	-1.82	Destabilizing	0.742	D	0.687	prob.neutral	None	None	None	None	N
M/R	0.4243	ambiguous	0.4442	ambiguous	-1.605	Destabilizing	0.521	D	0.649	neutral	N	0.405134653	None	None	N
M/S	0.3546	ambiguous	0.4071	ambiguous	-2.528	Highly Destabilizing	0.742	D	0.658	neutral	None	None	None	None	N
M/T	0.1868	likely_benign	0.2158	benign	-2.273	Highly Destabilizing	0.684	D	0.653	neutral	N	0.469666135	None	None	N
M/V	0.1477	likely_benign	0.1552	benign	-1.874	Destabilizing	0.472	N	0.751	deleterious	N	0.47522667	None	None	N
M/W	0.8349	likely_pathogenic	0.8595	pathogenic	-1.327	Destabilizing	0.996	D	0.656	neutral	None	None	None	None	N
M/Y	0.7556	likely_pathogenic	0.7972	pathogenic	-1.409	Destabilizing	0.984	D	0.666	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.