TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7550	22873;22874;22875	chr2:178722015;178722014;178722013	chr2:179586742;179586741;179586740
N2AB	7233	21922;21923;21924	chr2:178722015;178722014;178722013	chr2:179586742;179586741;179586740
N2A	6306	19141;19142;19143	chr2:178722015;178722014;178722013	chr2:179586742;179586741;179586740
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-60
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1502
• 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
K/N	rs1460815999	-1.266	1.0	N	0.651	0.421	0.306377322295	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
K/N	rs1460815999	-1.266	1.0	N	0.651	0.421	0.306377322295	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1460815999	-1.266	1.0	N	0.651	0.421	0.306377322295	gnomAD-4.0.0	4.33862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93427E-06	0	0
K/Q	rs772516390	-1.151	0.999	N	0.628	0.447	0.346768085243	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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
K/A	0.9677	likely_pathogenic	0.9809	pathogenic	-1.252	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	N
K/C	0.9736	likely_pathogenic	0.9765	pathogenic	-1.341	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/D	0.9965	likely_pathogenic	0.9978	pathogenic	-0.876	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/E	0.9235	likely_pathogenic	0.9568	pathogenic	-0.674	Destabilizing	0.997	D	0.521	neutral	D	0.522043791	None	None	N
K/F	0.9805	likely_pathogenic	0.9861	pathogenic	-0.939	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/G	0.9854	likely_pathogenic	0.9911	pathogenic	-1.682	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
K/H	0.7501	likely_pathogenic	0.7921	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/I	0.938	likely_pathogenic	0.9521	pathogenic	-0.08	Destabilizing	0.999	D	0.785	deleterious	N	0.492632456	None	None	N
K/L	0.8958	likely_pathogenic	0.9264	pathogenic	-0.08	Destabilizing	0.997	D	0.664	neutral	None	None	None	None	N
K/M	0.859	likely_pathogenic	0.8934	pathogenic	-0.134	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/N	0.9845	likely_pathogenic	0.9896	pathogenic	-1.234	Destabilizing	1.0	D	0.651	neutral	N	0.506648561	None	None	N
K/P	0.9978	likely_pathogenic	0.9987	pathogenic	-0.444	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/Q	0.6533	likely_pathogenic	0.7526	pathogenic	-1.149	Destabilizing	0.999	D	0.628	neutral	N	0.500545721	None	None	N
K/R	0.0952	likely_benign	0.117	benign	-0.952	Destabilizing	0.869	D	0.373	neutral	N	0.48012827	None	None	N
K/S	0.984	likely_pathogenic	0.991	pathogenic	-1.962	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	N
K/T	0.9532	likely_pathogenic	0.9754	pathogenic	-1.507	Destabilizing	1.0	D	0.67	neutral	N	0.506395071	None	None	N
K/V	0.9074	likely_pathogenic	0.9303	pathogenic	-0.444	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.9652	likely_pathogenic	0.9748	pathogenic	-0.821	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/Y	0.9527	likely_pathogenic	0.9593	pathogenic	-0.484	Destabilizing	0.999	D	0.768	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.