TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15338	46237;46238;46239	chr2:178620509;178620508;178620507	chr2:179485236;179485235;179485234
N2AB	13697	41314;41315;41316	chr2:178620509;178620508;178620507	chr2:179485236;179485235;179485234
N2A	12770	38533;38534;38535	chr2:178620509;178620508;178620507	chr2:179485236;179485235;179485234
N2B	6273	19042;19043;19044	chr2:178620509;178620508;178620507	chr2:179485236;179485235;179485234
Novex-1	6398	19417;19418;19419	chr2:178620509;178620508;178620507	chr2:179485236;179485235;179485234
Novex-2	6465	19618;19619;19620	chr2:178620509;178620508;178620507	chr2:179485236;179485235;179485234
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: Ig-105
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.3879
• 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/S	None	None	1.0	D	0.673	0.546	0.223847106136	gnomAD-4.0.0	6.84774E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0002E-07	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	0.4515	ambiguous	0.3774	ambiguous	-0.266	Destabilizing	1.0	D	0.581	neutral	D	0.590771935	None	None	N
G/C	0.5477	ambiguous	0.454	ambiguous	-0.881	Destabilizing	1.0	D	0.725	prob.delet.	D	0.656368091	None	None	N
G/D	0.342	ambiguous	0.2692	benign	-0.695	Destabilizing	1.0	D	0.653	neutral	N	0.498505864	None	None	N
G/E	0.4261	ambiguous	0.3289	benign	-0.87	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
G/F	0.9097	likely_pathogenic	0.8742	pathogenic	-1.051	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
G/H	0.6521	likely_pathogenic	0.574	pathogenic	-0.441	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
G/I	0.825	likely_pathogenic	0.7321	pathogenic	-0.486	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/K	0.5814	likely_pathogenic	0.4904	ambiguous	-0.778	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
G/L	0.8391	likely_pathogenic	0.7963	pathogenic	-0.486	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
G/M	0.8155	likely_pathogenic	0.7699	pathogenic	-0.486	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/N	0.3985	ambiguous	0.3615	ambiguous	-0.444	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
G/P	0.992	likely_pathogenic	0.9863	pathogenic	-0.383	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
G/Q	0.482	ambiguous	0.4195	ambiguous	-0.76	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
G/R	0.4706	ambiguous	0.3576	ambiguous	-0.289	Destabilizing	1.0	D	0.692	prob.neutral	D	0.65370118	None	None	N
G/S	0.2283	likely_benign	0.1869	benign	-0.554	Destabilizing	1.0	D	0.673	neutral	D	0.588194396	None	None	N
G/T	0.5185	ambiguous	0.4461	ambiguous	-0.667	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
G/V	0.7615	likely_pathogenic	0.6411	pathogenic	-0.383	Destabilizing	1.0	D	0.684	prob.neutral	D	0.656368091	None	None	N
G/W	0.7636	likely_pathogenic	0.6556	pathogenic	-1.174	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/Y	0.814	likely_pathogenic	0.7345	pathogenic	-0.844	Destabilizing	1.0	D	0.712	prob.delet.	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.