TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23266	70021;70022;70023	chr2:178576336;178576335;178576334	chr2:179441063;179441062;179441061
N2AB	21625	65098;65099;65100	chr2:178576336;178576335;178576334	chr2:179441063;179441062;179441061
N2A	20698	62317;62318;62319	chr2:178576336;178576335;178576334	chr2:179441063;179441062;179441061
N2B	14201	42826;42827;42828	chr2:178576336;178576335;178576334	chr2:179441063;179441062;179441061
Novex-1	14326	43201;43202;43203	chr2:178576336;178576335;178576334	chr2:179441063;179441062;179441061
Novex-2	14393	43402;43403;43404	chr2:178576336;178576335;178576334	chr2:179441063;179441062;179441061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-57
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.558
• 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
Y/S	None	None	0.967	N	0.582	0.486	0.344945010812	gnomAD-4.0.0	1.71684E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.01448E-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
Y/A	0.8804	likely_pathogenic	0.8082	pathogenic	-0.789	Destabilizing	0.916	D	0.505	neutral	None	None	None	None	I
Y/C	0.5157	ambiguous	0.3955	ambiguous	0.136	Stabilizing	0.999	D	0.667	neutral	N	0.464755285	None	None	I
Y/D	0.7044	likely_pathogenic	0.5374	ambiguous	0.946	Stabilizing	0.967	D	0.657	neutral	N	0.395685664	None	None	I
Y/E	0.9385	likely_pathogenic	0.8881	pathogenic	0.929	Stabilizing	0.975	D	0.548	neutral	None	None	None	None	I
Y/F	0.2053	likely_benign	0.1948	benign	-0.394	Destabilizing	0.944	D	0.525	neutral	N	0.483267363	None	None	I
Y/G	0.7918	likely_pathogenic	0.6933	pathogenic	-0.987	Destabilizing	0.975	D	0.589	neutral	None	None	None	None	I
Y/H	0.6069	likely_pathogenic	0.4814	ambiguous	0.144	Stabilizing	0.056	N	0.264	neutral	N	0.423565699	None	None	I
Y/I	0.8783	likely_pathogenic	0.8334	pathogenic	-0.287	Destabilizing	0.987	D	0.635	neutral	None	None	None	None	I
Y/K	0.9052	likely_pathogenic	0.8562	pathogenic	0.206	Stabilizing	0.975	D	0.627	neutral	None	None	None	None	I
Y/L	0.8241	likely_pathogenic	0.774	pathogenic	-0.287	Destabilizing	0.916	D	0.563	neutral	None	None	None	None	I
Y/M	0.8986	likely_pathogenic	0.8527	pathogenic	-0.066	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
Y/N	0.5858	likely_pathogenic	0.4274	ambiguous	0.068	Stabilizing	0.967	D	0.637	neutral	N	0.447114562	None	None	I
Y/P	0.9853	likely_pathogenic	0.9806	pathogenic	-0.435	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	I
Y/Q	0.8926	likely_pathogenic	0.8233	pathogenic	0.084	Stabilizing	0.975	D	0.639	neutral	None	None	None	None	I
Y/R	0.7963	likely_pathogenic	0.7135	pathogenic	0.503	Stabilizing	0.975	D	0.64	neutral	None	None	None	None	I
Y/S	0.6016	likely_pathogenic	0.4272	ambiguous	-0.411	Destabilizing	0.967	D	0.582	neutral	N	0.434107979	None	None	I
Y/T	0.8379	likely_pathogenic	0.7408	pathogenic	-0.338	Destabilizing	0.987	D	0.635	neutral	None	None	None	None	I
Y/V	0.7874	likely_pathogenic	0.7113	pathogenic	-0.435	Destabilizing	0.987	D	0.551	neutral	None	None	None	None	I
Y/W	0.6414	likely_pathogenic	0.6052	pathogenic	-0.465	Destabilizing	0.999	D	0.615	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.