TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33474	100645;100646;100647	chr2:178536327;178536326;178536325	chr2:179401054;179401053;179401052
N2AB	31833	95722;95723;95724	chr2:178536327;178536326;178536325	chr2:179401054;179401053;179401052
N2A	30906	92941;92942;92943	chr2:178536327;178536326;178536325	chr2:179401054;179401053;179401052
N2B	24409	73450;73451;73452	chr2:178536327;178536326;178536325	chr2:179401054;179401053;179401052
Novex-1	24534	73825;73826;73827	chr2:178536327;178536326;178536325	chr2:179401054;179401053;179401052
Novex-2	24601	74026;74027;74028	chr2:178536327;178536326;178536325	chr2:179401054;179401053;179401052
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-131
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.2013
• 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
G/R	rs1221430009	None	1.0	D	0.927	0.865	0.719018106523	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
G/R	rs1221430009	None	1.0	D	0.927	0.865	0.719018106523	gnomAD-4.0.0	6.57056E-06	None	None	None	None	I	None	0	6.5445E-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
G/A	0.7104	likely_pathogenic	0.6972	pathogenic	-0.596	Destabilizing	1.0	D	0.765	deleterious	D	0.542135596	None	None	I
G/C	0.8514	likely_pathogenic	0.8187	pathogenic	-0.95	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
G/D	0.8962	likely_pathogenic	0.8756	pathogenic	-1.05	Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	I
G/E	0.9061	likely_pathogenic	0.8831	pathogenic	-1.212	Destabilizing	1.0	D	0.918	deleterious	D	0.560239851	None	None	I
G/F	0.9711	likely_pathogenic	0.9681	pathogenic	-1.281	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/H	0.9767	likely_pathogenic	0.9702	pathogenic	-0.8	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/I	0.9575	likely_pathogenic	0.9478	pathogenic	-0.667	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	I
G/K	0.9643	likely_pathogenic	0.9569	pathogenic	-1.032	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/L	0.9662	likely_pathogenic	0.9601	pathogenic	-0.667	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
G/M	0.9745	likely_pathogenic	0.9655	pathogenic	-0.494	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
G/N	0.9262	likely_pathogenic	0.9032	pathogenic	-0.662	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/P	0.9974	likely_pathogenic	0.997	pathogenic	-0.61	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	I
G/Q	0.9321	likely_pathogenic	0.9169	pathogenic	-1.027	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	I
G/R	0.9175	likely_pathogenic	0.9052	pathogenic	-0.495	Destabilizing	1.0	D	0.927	deleterious	D	0.560493341	None	None	I
G/S	0.5668	likely_pathogenic	0.5175	ambiguous	-0.803	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/T	0.88	likely_pathogenic	0.8471	pathogenic	-0.909	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/V	0.9241	likely_pathogenic	0.9083	pathogenic	-0.61	Destabilizing	1.0	D	0.905	deleterious	D	0.528652924	None	None	I
G/W	0.9479	likely_pathogenic	0.9433	pathogenic	-1.394	Destabilizing	1.0	D	0.892	deleterious	D	0.561507299	None	None	I
G/Y	0.9619	likely_pathogenic	0.9528	pathogenic	-1.072	Destabilizing	1.0	D	0.906	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.