TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19580	58963;58964;58965	chr2:178593470;178593469;178593468	chr2:179458197;179458196;179458195
N2AB	17939	54040;54041;54042	chr2:178593470;178593469;178593468	chr2:179458197;179458196;179458195
N2A	17012	51259;51260;51261	chr2:178593470;178593469;178593468	chr2:179458197;179458196;179458195
N2B	10515	31768;31769;31770	chr2:178593470;178593469;178593468	chr2:179458197;179458196;179458195
Novex-1	10640	32143;32144;32145	chr2:178593470;178593469;178593468	chr2:179458197;179458196;179458195
Novex-2	10707	32344;32345;32346	chr2:178593470;178593469;178593468	chr2:179458197;179458196;179458195
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-30
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.164
• 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
P/L	None	None	1.0	D	0.815	0.614	0.796498930371	gnomAD-4.0.0	1.60459E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86707E-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
P/A	0.7574	likely_pathogenic	0.7677	pathogenic	-1.824	Destabilizing	0.999	D	0.835	deleterious	D	0.620984605	None	None	N
P/C	0.9795	likely_pathogenic	0.98	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/D	0.9991	likely_pathogenic	0.9989	pathogenic	-3.523	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/E	0.9966	likely_pathogenic	0.9963	pathogenic	-3.407	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/F	0.9994	likely_pathogenic	0.9993	pathogenic	-0.992	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/G	0.9847	likely_pathogenic	0.9854	pathogenic	-2.176	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/H	0.9961	likely_pathogenic	0.9957	pathogenic	-1.559	Destabilizing	1.0	D	0.763	deleterious	D	0.658968526	None	None	N
P/I	0.9904	likely_pathogenic	0.9898	pathogenic	-0.877	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
P/K	0.9976	likely_pathogenic	0.9976	pathogenic	-1.703	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/L	0.9609	likely_pathogenic	0.9549	pathogenic	-0.877	Destabilizing	1.0	D	0.815	deleterious	D	0.642747361	None	None	N
P/M	0.9944	likely_pathogenic	0.9936	pathogenic	-1.275	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
P/N	0.9986	likely_pathogenic	0.9983	pathogenic	-2.122	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/Q	0.9935	likely_pathogenic	0.9929	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/R	0.9904	likely_pathogenic	0.9906	pathogenic	-1.327	Destabilizing	1.0	D	0.829	deleterious	D	0.642747361	None	None	N
P/S	0.9598	likely_pathogenic	0.9556	pathogenic	-2.442	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.642545557	None	None	N
P/T	0.9577	likely_pathogenic	0.9583	pathogenic	-2.225	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.642747361	None	None	N
P/V	0.9702	likely_pathogenic	0.9699	pathogenic	-1.169	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9995	pathogenic	-1.382	Destabilizing	1.0	D	0.707	prob.delet.	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9993	pathogenic	-1.123	Destabilizing	1.0	D	0.799	deleterious	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.