TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22919	68980;68981;68982	chr2:178577671;178577670;178577669	chr2:179442398;179442397;179442396
N2AB	21278	64057;64058;64059	chr2:178577671;178577670;178577669	chr2:179442398;179442397;179442396
N2A	20351	61276;61277;61278	chr2:178577671;178577670;178577669	chr2:179442398;179442397;179442396
N2B	13854	41785;41786;41787	chr2:178577671;178577670;178577669	chr2:179442398;179442397;179442396
Novex-1	13979	42160;42161;42162	chr2:178577671;178577670;178577669	chr2:179442398;179442397;179442396
Novex-2	14046	42361;42362;42363	chr2:178577671;178577670;178577669	chr2:179442398;179442397;179442396
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-54
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2124
• 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
K/E	None	None	0.025	N	0.377	0.199	0.221734844693	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.914	likely_pathogenic	0.9173	pathogenic	-0.734	Destabilizing	0.916	D	0.554	neutral	None	None	None	None	N
K/C	0.9067	likely_pathogenic	0.9137	pathogenic	-1.204	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
K/D	0.9924	likely_pathogenic	0.9933	pathogenic	-0.822	Destabilizing	0.845	D	0.598	neutral	None	None	None	None	N
K/E	0.789	likely_pathogenic	0.7989	pathogenic	-0.733	Destabilizing	0.025	N	0.377	neutral	N	0.483520866	None	None	N
K/F	0.9749	likely_pathogenic	0.9784	pathogenic	-0.911	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
K/G	0.9585	likely_pathogenic	0.9616	pathogenic	-1.034	Destabilizing	0.916	D	0.638	neutral	None	None	None	None	N
K/H	0.7736	likely_pathogenic	0.7708	pathogenic	-1.451	Destabilizing	0.997	D	0.673	neutral	None	None	None	None	N
K/I	0.7898	likely_pathogenic	0.7992	pathogenic	0.023	Stabilizing	0.987	D	0.763	deleterious	None	None	None	None	N
K/L	0.8523	likely_pathogenic	0.8452	pathogenic	0.023	Stabilizing	0.975	D	0.669	neutral	None	None	None	None	N
K/M	0.7057	likely_pathogenic	0.7046	pathogenic	0.029	Stabilizing	0.999	D	0.654	neutral	N	0.47687574	None	None	N
K/N	0.9742	likely_pathogenic	0.9759	pathogenic	-0.731	Destabilizing	0.967	D	0.579	neutral	N	0.481408417	None	None	N
K/P	0.9957	likely_pathogenic	0.9955	pathogenic	-0.202	Destabilizing	0.987	D	0.713	prob.delet.	None	None	None	None	N
K/Q	0.4189	ambiguous	0.4228	ambiguous	-0.981	Destabilizing	0.935	D	0.585	neutral	N	0.471898536	None	None	N
K/R	0.0903	likely_benign	0.0901	benign	-0.495	Destabilizing	0.056	N	0.354	neutral	N	0.457891703	None	None	N
K/S	0.9554	likely_pathogenic	0.9572	pathogenic	-1.373	Destabilizing	0.916	D	0.489	neutral	None	None	None	None	N
K/T	0.7556	likely_pathogenic	0.7664	pathogenic	-1.094	Destabilizing	0.967	D	0.669	neutral	N	0.521231105	None	None	N
K/V	0.7029	likely_pathogenic	0.7212	pathogenic	-0.202	Destabilizing	0.987	D	0.673	neutral	None	None	None	None	N
K/W	0.944	likely_pathogenic	0.9479	pathogenic	-0.798	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
K/Y	0.9356	likely_pathogenic	0.9434	pathogenic	-0.37	Destabilizing	0.996	D	0.729	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.