TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6269	19030;19031;19032	chr2:178729351;178729350;178729349	chr2:179594078;179594077;179594076
N2AB	5952	18079;18080;18081	chr2:178729351;178729350;178729349	chr2:179594078;179594077;179594076
N2A	5025	15298;15299;15300	chr2:178729351;178729350;178729349	chr2:179594078;179594077;179594076
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-46
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1048
• 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
Y/C	None	None	1.0	D	0.879	0.873	0.894440237169	gnomAD-4.0.0	1.36863E-06	None	None	None	None	N	None	0	2.23734E-05	None	0	0	None	0	0	8.99575E-07	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	0.9947	likely_pathogenic	0.9963	pathogenic	-2.792	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/C	0.9473	likely_pathogenic	0.967	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.652959066	None	None	N
Y/D	0.9976	likely_pathogenic	0.9981	pathogenic	-3.51	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.652959066	None	None	N
Y/E	0.9985	likely_pathogenic	0.9989	pathogenic	-3.265	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/F	0.1888	likely_benign	0.2267	benign	-1.118	Destabilizing	0.999	D	0.683	prob.neutral	D	0.565766957	None	None	N
Y/G	0.9908	likely_pathogenic	0.992	pathogenic	-3.253	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/H	0.9771	likely_pathogenic	0.9846	pathogenic	-2.429	Highly Destabilizing	1.0	D	0.784	deleterious	D	0.652757262	None	None	N
Y/I	0.8514	likely_pathogenic	0.8999	pathogenic	-1.254	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/K	0.9983	likely_pathogenic	0.9989	pathogenic	-2.432	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.8622	likely_pathogenic	0.893	pathogenic	-1.254	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
Y/M	0.9527	likely_pathogenic	0.9675	pathogenic	-1.315	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/N	0.981	likely_pathogenic	0.9852	pathogenic	-3.397	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.652959066	None	None	N
Y/P	0.9992	likely_pathogenic	0.9993	pathogenic	-1.785	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/Q	0.998	likely_pathogenic	0.9987	pathogenic	-2.969	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/R	0.9956	likely_pathogenic	0.997	pathogenic	-2.541	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/S	0.9912	likely_pathogenic	0.9933	pathogenic	-3.709	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.652959066	None	None	N
Y/T	0.994	likely_pathogenic	0.9958	pathogenic	-3.315	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.8591	likely_pathogenic	0.8972	pathogenic	-1.785	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
Y/W	0.8555	likely_pathogenic	0.8801	pathogenic	-0.48	Destabilizing	1.0	D	0.778	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.