TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23116	69571;69572;69573	chr2:178576989;178576988;178576987	chr2:179441716;179441715;179441714
N2AB	21475	64648;64649;64650	chr2:178576989;178576988;178576987	chr2:179441716;179441715;179441714
N2A	20548	61867;61868;61869	chr2:178576989;178576988;178576987	chr2:179441716;179441715;179441714
N2B	14051	42376;42377;42378	chr2:178576989;178576988;178576987	chr2:179441716;179441715;179441714
Novex-1	14176	42751;42752;42753	chr2:178576989;178576988;178576987	chr2:179441716;179441715;179441714
Novex-2	14243	42952;42953;42954	chr2:178576989;178576988;178576987	chr2:179441716;179441715;179441714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-55
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.0877
• 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/D	rs2154173466	None	1.0	D	0.85	0.729	0.87120463873	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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	0.9183	likely_pathogenic	0.9105	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
A/D	0.9979	likely_pathogenic	0.9986	pathogenic	-3.121	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.667062184	None	None	N
A/E	0.9976	likely_pathogenic	0.9985	pathogenic	-2.91	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
A/F	0.9955	likely_pathogenic	0.9958	pathogenic	-0.892	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/G	0.2623	likely_benign	0.2218	benign	-2.103	Highly Destabilizing	1.0	D	0.595	neutral	D	0.57560003	None	None	N
A/H	0.9986	likely_pathogenic	0.999	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/I	0.9901	likely_pathogenic	0.9917	pathogenic	-0.456	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/K	0.9993	likely_pathogenic	0.9996	pathogenic	-1.549	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/L	0.9621	likely_pathogenic	0.9669	pathogenic	-0.456	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
A/M	0.9858	likely_pathogenic	0.9863	pathogenic	-1.028	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/N	0.9951	likely_pathogenic	0.9962	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
A/P	0.8206	likely_pathogenic	0.8849	pathogenic	-0.822	Destabilizing	1.0	D	0.867	deleterious	D	0.634185885	None	None	N
A/Q	0.9953	likely_pathogenic	0.9966	pathogenic	-1.829	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/R	0.996	likely_pathogenic	0.9975	pathogenic	-1.549	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/S	0.4907	ambiguous	0.5042	ambiguous	-2.391	Highly Destabilizing	1.0	D	0.592	neutral	D	0.585906356	None	None	N
A/T	0.904	likely_pathogenic	0.9226	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.789	deleterious	D	0.633782276	None	None	N
A/V	0.9334	likely_pathogenic	0.9441	pathogenic	-0.822	Destabilizing	1.0	D	0.696	prob.neutral	D	0.628069241	None	None	N
A/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.517	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
A/Y	0.9982	likely_pathogenic	0.9985	pathogenic	-1.138	Destabilizing	1.0	D	0.885	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.