TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18433	55522;55523;55524	chr2:178601887;178601886;178601885	chr2:179466614;179466613;179466612
N2AB	16792	50599;50600;50601	chr2:178601887;178601886;178601885	chr2:179466614;179466613;179466612
N2A	15865	47818;47819;47820	chr2:178601887;178601886;178601885	chr2:179466614;179466613;179466612
N2B	9368	28327;28328;28329	chr2:178601887;178601886;178601885	chr2:179466614;179466613;179466612
Novex-1	9493	28702;28703;28704	chr2:178601887;178601886;178601885	chr2:179466614;179466613;179466612
Novex-2	9560	28903;28904;28905	chr2:178601887;178601886;178601885	chr2:179466614;179466613;179466612
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-115
• Domain position: 52
• Structural Position: 102
• Q(SASA): 0.1649
• 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
A/T	rs2053557019	None	0.811	N	0.533	0.216	0.222439326576	gnomAD-4.0.0	1.59686E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86462E-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
A/C	0.4365	ambiguous	0.3646	ambiguous	-1.125	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
A/D	0.9432	likely_pathogenic	0.9474	pathogenic	-2.303	Highly Destabilizing	0.976	D	0.752	deleterious	None	None	None	None	N
A/E	0.935	likely_pathogenic	0.9387	pathogenic	-2.225	Highly Destabilizing	0.896	D	0.662	neutral	D	0.529133805	None	None	N
A/F	0.7912	likely_pathogenic	0.7612	pathogenic	-1.081	Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
A/G	0.2186	likely_benign	0.2032	benign	-1.633	Destabilizing	0.811	D	0.556	neutral	N	0.50975861	None	None	N
A/H	0.9316	likely_pathogenic	0.9286	pathogenic	-2.057	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
A/I	0.5293	ambiguous	0.4949	ambiguous	-0.348	Destabilizing	0.988	D	0.754	deleterious	None	None	None	None	N
A/K	0.9747	likely_pathogenic	0.9748	pathogenic	-1.863	Destabilizing	0.132	N	0.409	neutral	None	None	None	None	N
A/L	0.5269	ambiguous	0.5065	ambiguous	-0.348	Destabilizing	0.919	D	0.651	neutral	None	None	None	None	N
A/M	0.5773	likely_pathogenic	0.5325	ambiguous	-0.213	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
A/N	0.8939	likely_pathogenic	0.8914	pathogenic	-1.772	Destabilizing	0.976	D	0.757	deleterious	None	None	None	None	N
A/P	0.9513	likely_pathogenic	0.9555	pathogenic	-0.612	Destabilizing	0.984	D	0.737	prob.delet.	N	0.51826345	None	None	N
A/Q	0.9095	likely_pathogenic	0.9059	pathogenic	-1.776	Destabilizing	0.976	D	0.754	deleterious	None	None	None	None	N
A/R	0.9503	likely_pathogenic	0.9525	pathogenic	-1.587	Destabilizing	0.952	D	0.73	prob.delet.	None	None	None	None	N
A/S	0.1403	likely_benign	0.1158	benign	-2.084	Highly Destabilizing	0.103	N	0.355	neutral	N	0.439186591	None	None	N
A/T	0.181	likely_benign	0.1742	benign	-1.911	Destabilizing	0.811	D	0.533	neutral	N	0.503659357	None	None	N
A/V	0.2657	likely_benign	0.2579	benign	-0.612	Destabilizing	0.896	D	0.569	neutral	N	0.465138254	None	None	N
A/W	0.9564	likely_pathogenic	0.946	pathogenic	-1.704	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
A/Y	0.8761	likely_pathogenic	0.8584	pathogenic	-1.247	Destabilizing	0.996	D	0.795	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.