TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8908	26947;26948;26949	chr2:178713936;178713935;178713934	chr2:179578663;179578662;179578661
N2AB	8591	25996;25997;25998	chr2:178713936;178713935;178713934	chr2:179578663;179578662;179578661
N2A	7664	23215;23216;23217	chr2:178713936;178713935;178713934	chr2:179578663;179578662;179578661
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-74
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.7318
• 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	None	None	0.98	N	0.463	0.273	0.40146981186	gnomAD-4.0.0	1.59176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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	0.141	likely_benign	0.1414	benign	-0.407	Destabilizing	0.835	D	0.49	neutral	N	0.460311225	None	None	N
V/C	0.8491	likely_pathogenic	0.849	pathogenic	-0.856	Destabilizing	1.0	D	0.554	neutral	None	None	None	None	N
V/D	0.7285	likely_pathogenic	0.7208	pathogenic	-0.449	Destabilizing	0.989	D	0.623	neutral	N	0.512385548	None	None	N
V/E	0.5362	ambiguous	0.5158	ambiguous	-0.57	Destabilizing	0.991	D	0.537	neutral	None	None	None	None	N
V/F	0.1913	likely_benign	0.2069	benign	-0.803	Destabilizing	0.977	D	0.479	neutral	D	0.522207832	None	None	N
V/G	0.3913	ambiguous	0.4099	ambiguous	-0.453	Destabilizing	0.961	D	0.553	neutral	D	0.524613419	None	None	N
V/H	0.7403	likely_pathogenic	0.7409	pathogenic	-0.041	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
V/I	0.0948	likely_benign	0.097	benign	-0.425	Destabilizing	0.98	D	0.463	neutral	N	0.521034396	None	None	N
V/K	0.6572	likely_pathogenic	0.6323	pathogenic	-0.436	Destabilizing	0.991	D	0.542	neutral	None	None	None	None	N
V/L	0.3149	likely_benign	0.3326	benign	-0.425	Destabilizing	0.91	D	0.509	neutral	N	0.497541461	None	None	N
V/M	0.2051	likely_benign	0.2084	benign	-0.617	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	N
V/N	0.575	likely_pathogenic	0.5758	pathogenic	-0.257	Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
V/P	0.9216	likely_pathogenic	0.9322	pathogenic	-0.392	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	N
V/Q	0.5469	ambiguous	0.5377	ambiguous	-0.481	Destabilizing	0.996	D	0.602	neutral	None	None	None	None	N
V/R	0.5331	ambiguous	0.5132	ambiguous	0.038	Stabilizing	0.996	D	0.636	neutral	None	None	None	None	N
V/S	0.2895	likely_benign	0.3053	benign	-0.554	Destabilizing	0.746	D	0.471	neutral	None	None	None	None	N
V/T	0.2476	likely_benign	0.2428	benign	-0.587	Destabilizing	0.942	D	0.445	neutral	None	None	None	None	N
V/W	0.8895	likely_pathogenic	0.8872	pathogenic	-0.842	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
V/Y	0.6567	likely_pathogenic	0.687	pathogenic	-0.582	Destabilizing	0.503	D	0.391	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.