TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15829	47710;47711;47712	chr2:178617866;178617865;178617864	chr2:179482593;179482592;179482591
N2AB	14188	42787;42788;42789	chr2:178617866;178617865;178617864	chr2:179482593;179482592;179482591
N2A	13261	40006;40007;40008	chr2:178617866;178617865;178617864	chr2:179482593;179482592;179482591
N2B	6764	20515;20516;20517	chr2:178617866;178617865;178617864	chr2:179482593;179482592;179482591
Novex-1	6889	20890;20891;20892	chr2:178617866;178617865;178617864	chr2:179482593;179482592;179482591
Novex-2	6956	21091;21092;21093	chr2:178617866;178617865;178617864	chr2:179482593;179482592;179482591
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: Fn3-2
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0954
• 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/H	None	None	1.0	D	0.84	0.869	0.854435163953	gnomAD-4.0.0	1.59363E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-05	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	0.9645	likely_pathogenic	0.9662	pathogenic	-2.975	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/C	0.6596	likely_pathogenic	0.686	pathogenic	-1.476	Destabilizing	1.0	D	0.875	deleterious	D	0.773711393	None	None	N
Y/D	0.9854	likely_pathogenic	0.9876	pathogenic	-3.434	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.804567791	None	None	N
Y/E	0.9936	likely_pathogenic	0.9937	pathogenic	-3.209	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/F	0.1988	likely_benign	0.2289	benign	-1.046	Destabilizing	0.999	D	0.757	deleterious	D	0.693255757	None	None	N
Y/G	0.9626	likely_pathogenic	0.9622	pathogenic	-3.398	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/H	0.8497	likely_pathogenic	0.8894	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.804567791	None	None	N
Y/I	0.8328	likely_pathogenic	0.8191	pathogenic	-1.558	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9801	likely_pathogenic	0.9799	pathogenic	-2.108	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/L	0.8461	likely_pathogenic	0.8324	pathogenic	-1.558	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
Y/M	0.9063	likely_pathogenic	0.9104	pathogenic	-1.255	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/N	0.8631	likely_pathogenic	0.8718	pathogenic	-2.958	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.773999782	None	None	N
Y/P	0.9987	likely_pathogenic	0.9986	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/Q	0.9799	likely_pathogenic	0.9825	pathogenic	-2.656	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.9574	likely_pathogenic	0.959	pathogenic	-1.997	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9419	likely_pathogenic	0.9453	pathogenic	-3.252	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.754855634	None	None	N
Y/T	0.9625	likely_pathogenic	0.9588	pathogenic	-2.903	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/V	0.7137	likely_pathogenic	0.6856	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/W	0.8301	likely_pathogenic	0.86	pathogenic	-0.341	Destabilizing	1.0	D	0.817	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.