TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25636	77131;77132;77133	chr2:178569226;178569225;178569224	chr2:179433953;179433952;179433951
N2AB	23995	72208;72209;72210	chr2:178569226;178569225;178569224	chr2:179433953;179433952;179433951
N2A	23068	69427;69428;69429	chr2:178569226;178569225;178569224	chr2:179433953;179433952;179433951
N2B	16571	49936;49937;49938	chr2:178569226;178569225;178569224	chr2:179433953;179433952;179433951
Novex-1	16696	50311;50312;50313	chr2:178569226;178569225;178569224	chr2:179433953;179433952;179433951
Novex-2	16763	50512;50513;50514	chr2:178569226;178569225;178569224	chr2:179433953;179433952;179433951
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: Fn3-74
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1407
• 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	rs2154167623	None	1.0	D	0.811	0.776	0.889359714302	gnomAD-4.0.0	1.61512E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89919E-06	0	0
Y/S	None	None	1.0	D	0.833	0.769	0.908842003314	gnomAD-4.0.0	1.61512E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46447E-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	0.9939	likely_pathogenic	0.9938	pathogenic	-3.792	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
Y/C	0.8742	likely_pathogenic	0.8818	pathogenic	-2.415	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.65326267	None	None	N
Y/D	0.9945	likely_pathogenic	0.9948	pathogenic	-3.974	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.66968564	None	None	N
Y/E	0.9989	likely_pathogenic	0.9989	pathogenic	-3.776	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/F	0.1641	likely_benign	0.1823	benign	-1.443	Destabilizing	0.18	N	0.454	neutral	D	0.578709251	None	None	N
Y/G	0.9879	likely_pathogenic	0.9883	pathogenic	-4.177	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/H	0.9472	likely_pathogenic	0.9479	pathogenic	-2.724	Highly Destabilizing	1.0	D	0.741	deleterious	D	0.643976084	None	None	N
Y/I	0.9531	likely_pathogenic	0.9524	pathogenic	-2.479	Highly Destabilizing	0.981	D	0.755	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.998	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/L	0.9245	likely_pathogenic	0.9232	pathogenic	-2.479	Highly Destabilizing	0.938	D	0.705	prob.neutral	None	None	None	None	N
Y/M	0.972	likely_pathogenic	0.9736	pathogenic	-2.31	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/N	0.961	likely_pathogenic	0.9608	pathogenic	-3.339	Highly Destabilizing	1.0	D	0.834	deleterious	D	0.66968564	None	None	N
Y/P	0.9994	likely_pathogenic	0.9993	pathogenic	-2.936	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/Q	0.9966	likely_pathogenic	0.9968	pathogenic	-3.122	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
Y/R	0.992	likely_pathogenic	0.9925	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/S	0.9775	likely_pathogenic	0.9769	pathogenic	-3.687	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.66968564	None	None	N
Y/T	0.9902	likely_pathogenic	0.9897	pathogenic	-3.377	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/V	0.9272	likely_pathogenic	0.9248	pathogenic	-2.936	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
Y/W	0.8161	likely_pathogenic	0.8293	pathogenic	-0.664	Destabilizing	1.0	D	0.731	prob.delet.	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.