TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33291	100096;100097;100098	chr2:178537238;178537237;178537236	chr2:179401965;179401964;179401963
N2AB	31650	95173;95174;95175	chr2:178537238;178537237;178537236	chr2:179401965;179401964;179401963
N2A	30723	92392;92393;92394	chr2:178537238;178537237;178537236	chr2:179401965;179401964;179401963
N2B	24226	72901;72902;72903	chr2:178537238;178537237;178537236	chr2:179401965;179401964;179401963
Novex-1	24351	73276;73277;73278	chr2:178537238;178537237;178537236	chr2:179401965;179401964;179401963
Novex-2	24418	73477;73478;73479	chr2:178537238;178537237;178537236	chr2:179401965;179401964;179401963
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-130
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.295
• Predicted PPI site: I

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/Q	None	None	1.0	D	0.857	0.744	0.832103877067	gnomAD-4.0.0	1.6557E-06	None	None	None	None	I	None	0	2.44439E-05	None	0	0	None	0	0	0	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	0.8595	likely_pathogenic	0.8576	pathogenic	-1.358	Destabilizing	0.999	D	0.815	deleterious	D	0.631896343	None	None	I
P/C	0.9898	likely_pathogenic	0.9918	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/D	0.9992	likely_pathogenic	0.9992	pathogenic	-3.51	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
P/E	0.9974	likely_pathogenic	0.9975	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/F	0.9994	likely_pathogenic	0.9994	pathogenic	-0.858	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
P/G	0.99	likely_pathogenic	0.9914	pathogenic	-1.669	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
P/H	0.9978	likely_pathogenic	0.9981	pathogenic	-1.129	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/I	0.9867	likely_pathogenic	0.9884	pathogenic	-0.547	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
P/K	0.9982	likely_pathogenic	0.9981	pathogenic	-1.516	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/L	0.9672	likely_pathogenic	0.9704	pathogenic	-0.547	Destabilizing	1.0	D	0.797	deleterious	D	0.622781201	None	None	I
P/M	0.9947	likely_pathogenic	0.9958	pathogenic	-0.936	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
P/N	0.9987	likely_pathogenic	0.9988	pathogenic	-1.987	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
P/Q	0.9961	likely_pathogenic	0.9965	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.664540478	None	None	I
P/R	0.9938	likely_pathogenic	0.9934	pathogenic	-1.114	Destabilizing	1.0	D	0.845	deleterious	D	0.648319313	None	None	I
P/S	0.9881	likely_pathogenic	0.9899	pathogenic	-2.217	Highly Destabilizing	1.0	D	0.832	deleterious	D	0.664136869	None	None	I
P/T	0.9736	likely_pathogenic	0.9764	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.648319313	None	None	I
P/V	0.965	likely_pathogenic	0.967	pathogenic	-0.792	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
P/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.266	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/Y	0.9994	likely_pathogenic	0.9994	pathogenic	-0.929	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I

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.