TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5829	17710;17711;17712	chr2:178731180;178731179;178731178	chr2:179595907;179595906;179595905
N2AB	5512	16759;16760;16761	chr2:178731180;178731179;178731178	chr2:179595907;179595906;179595905
N2A	4585	13978;13979;13980	chr2:178731180;178731179;178731178	chr2:179595907;179595906;179595905
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-42
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.204
• 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
A/T	None	None	0.978	N	0.557	0.29	0.252162846088	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
A/V	None	None	0.978	N	0.528	0.262	0.38342384377	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
A/C	0.7906	likely_pathogenic	0.7975	pathogenic	-0.851	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
A/D	0.8812	likely_pathogenic	0.8721	pathogenic	-0.911	Destabilizing	0.997	D	0.781	deleterious	N	0.49930589	None	None	N
A/E	0.868	likely_pathogenic	0.8536	pathogenic	-0.964	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
A/F	0.8705	likely_pathogenic	0.8524	pathogenic	-0.926	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
A/G	0.2968	likely_benign	0.292	benign	-0.979	Destabilizing	0.989	D	0.487	neutral	N	0.510349603	None	None	N
A/H	0.9606	likely_pathogenic	0.9542	pathogenic	-1.175	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/I	0.5807	likely_pathogenic	0.5955	pathogenic	-0.287	Destabilizing	0.995	D	0.72	prob.delet.	None	None	None	None	N
A/K	0.965	likely_pathogenic	0.9622	pathogenic	-1.125	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
A/L	0.4726	ambiguous	0.4567	ambiguous	-0.287	Destabilizing	0.269	N	0.431	neutral	None	None	None	None	N
A/M	0.5378	ambiguous	0.5406	ambiguous	-0.287	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
A/N	0.8054	likely_pathogenic	0.7973	pathogenic	-0.814	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
A/P	0.2825	likely_benign	0.2803	benign	-0.399	Destabilizing	0.998	D	0.749	deleterious	N	0.409065101	None	None	N
A/Q	0.9116	likely_pathogenic	0.8974	pathogenic	-0.976	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
A/R	0.9482	likely_pathogenic	0.9414	pathogenic	-0.787	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
A/S	0.2526	likely_benign	0.2499	benign	-1.136	Destabilizing	0.889	D	0.35	neutral	N	0.447876992	None	None	N
A/T	0.223	likely_benign	0.2495	benign	-1.091	Destabilizing	0.978	D	0.557	neutral	N	0.4694257	None	None	N
A/V	0.2832	likely_benign	0.2995	benign	-0.399	Destabilizing	0.978	D	0.528	neutral	N	0.458272554	None	None	N
A/W	0.9819	likely_pathogenic	0.978	pathogenic	-1.24	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/Y	0.9366	likely_pathogenic	0.9244	pathogenic	-0.838	Destabilizing	1.0	D	0.792	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.