TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24619	74080;74081;74082	chr2:178572277;178572276;178572275	chr2:179437004;179437003;179437002
N2AB	22978	69157;69158;69159	chr2:178572277;178572276;178572275	chr2:179437004;179437003;179437002
N2A	22051	66376;66377;66378	chr2:178572277;178572276;178572275	chr2:179437004;179437003;179437002
N2B	15554	46885;46886;46887	chr2:178572277;178572276;178572275	chr2:179437004;179437003;179437002
Novex-1	15679	47260;47261;47262	chr2:178572277;178572276;178572275	chr2:179437004;179437003;179437002
Novex-2	15746	47461;47462;47463	chr2:178572277;178572276;178572275	chr2:179437004;179437003;179437002
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: Fn3-67
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1447
• 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	0.895	0.5	0.545519808136	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86105E-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	0.2189	likely_benign	0.1953	benign	-1.774	Destabilizing	1.0	D	0.844	deleterious	N	0.487403746	None	None	N
P/C	0.8354	likely_pathogenic	0.8023	pathogenic	-1.488	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/D	0.9895	likely_pathogenic	0.9856	pathogenic	-2.408	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/E	0.9316	likely_pathogenic	0.9136	pathogenic	-2.385	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/F	0.9507	likely_pathogenic	0.9246	pathogenic	-1.41	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/G	0.8884	likely_pathogenic	0.8725	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/H	0.8644	likely_pathogenic	0.8287	pathogenic	-1.566	Destabilizing	1.0	D	0.897	deleterious	D	0.52637002	None	None	N
P/I	0.791	likely_pathogenic	0.731	pathogenic	-0.939	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/K	0.9556	likely_pathogenic	0.9474	pathogenic	-1.438	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/L	0.5982	likely_pathogenic	0.5283	ambiguous	-0.939	Destabilizing	1.0	D	0.895	deleterious	D	0.537472836	None	None	N
P/M	0.816	likely_pathogenic	0.7668	pathogenic	-0.822	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
P/N	0.9582	likely_pathogenic	0.9454	pathogenic	-1.41	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/Q	0.7905	likely_pathogenic	0.7448	pathogenic	-1.619	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/R	0.8961	likely_pathogenic	0.8738	pathogenic	-0.893	Destabilizing	1.0	D	0.913	deleterious	N	0.501971888	None	None	N
P/S	0.5623	ambiguous	0.5037	ambiguous	-1.883	Destabilizing	1.0	D	0.851	deleterious	N	0.471586275	None	None	N
P/T	0.6451	likely_pathogenic	0.5635	ambiguous	-1.758	Destabilizing	1.0	D	0.848	deleterious	N	0.502732357	None	None	N
P/V	0.6258	likely_pathogenic	0.557	ambiguous	-1.187	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/W	0.9864	likely_pathogenic	0.9776	pathogenic	-1.636	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/Y	0.9568	likely_pathogenic	0.9345	pathogenic	-1.346	Destabilizing	1.0	D	0.931	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.