TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6975	21148;21149;21150	chr2:178724452;178724451;178724450	chr2:179589179;179589178;179589177
N2AB	6658	20197;20198;20199	chr2:178724452;178724451;178724450	chr2:179589179;179589178;179589177
N2A	5731	17416;17417;17418	chr2:178724452;178724451;178724450	chr2:179589179;179589178;179589177
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: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Ig-54
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.417
• 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/L	rs374493881	0.018	0.998	D	0.57	0.615	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	1.93874E-04	0	None	0	5.58E-05	None	0	None	0	2.67E-05	0
P/L	rs374493881	0.018	0.998	D	0.57	0.615	None	gnomAD-3.1.2	6.58E-05	None	None	None	None	I	None	1.93115E-04	0	0	0	1.92976E-04	None	0	0	0	0	4.78011E-04
P/L	rs374493881	0.018	0.998	D	0.57	0.615	None	gnomAD-4.0.0	2.54156E-05	None	None	None	None	I	None	2.40442E-04	0	None	0	2.22985E-05	None	0	1.64636E-04	1.27172E-05	3.29468E-05	4.80646E-05

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	0.3489	ambiguous	0.7333	pathogenic	-0.314	Destabilizing	0.911	D	0.369	neutral	D	0.529197399	None	None	I
P/C	0.9346	likely_pathogenic	0.9897	pathogenic	-0.7	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
P/D	0.8539	likely_pathogenic	0.9595	pathogenic	-0.388	Destabilizing	0.985	D	0.459	neutral	None	None	None	None	I
P/E	0.65	likely_pathogenic	0.9089	pathogenic	-0.51	Destabilizing	0.985	D	0.403	neutral	None	None	None	None	I
P/F	0.9516	likely_pathogenic	0.9923	pathogenic	-0.688	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	I
P/G	0.7446	likely_pathogenic	0.9139	pathogenic	-0.382	Destabilizing	0.985	D	0.451	neutral	None	None	None	None	I
P/H	0.7217	likely_pathogenic	0.9503	pathogenic	0.037	Stabilizing	1.0	D	0.541	neutral	None	None	None	None	I
P/I	0.8507	likely_pathogenic	0.9553	pathogenic	-0.282	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	I
P/K	0.6885	likely_pathogenic	0.9426	pathogenic	-0.371	Destabilizing	0.271	N	0.224	neutral	None	None	None	None	I
P/L	0.522	ambiguous	0.588	pathogenic	-0.282	Destabilizing	0.998	D	0.57	neutral	D	0.607599468	None	None	I
P/M	0.7952	likely_pathogenic	0.9515	pathogenic	-0.506	Destabilizing	1.0	D	0.54	neutral	None	None	None	None	I
P/N	0.8429	likely_pathogenic	0.9631	pathogenic	-0.132	Destabilizing	0.996	D	0.518	neutral	None	None	None	None	I
P/Q	0.5521	ambiguous	0.8959	pathogenic	-0.372	Destabilizing	0.998	D	0.461	neutral	D	0.532159914	None	None	I
P/R	0.5445	ambiguous	0.8948	pathogenic	0.115	Stabilizing	0.984	D	0.506	neutral	D	0.607195859	None	None	I
P/S	0.5518	ambiguous	0.8815	pathogenic	-0.429	Destabilizing	0.659	D	0.236	neutral	D	0.527373747	None	None	I
P/T	0.4463	ambiguous	0.7749	pathogenic	-0.462	Destabilizing	0.961	D	0.398	neutral	D	0.568192198	None	None	I
P/V	0.7011	likely_pathogenic	0.8942	pathogenic	-0.263	Destabilizing	0.993	D	0.499	neutral	None	None	None	None	I
P/W	0.96	likely_pathogenic	0.9931	pathogenic	-0.746	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
P/Y	0.9255	likely_pathogenic	0.9875	pathogenic	-0.462	Destabilizing	0.999	D	0.604	neutral	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.