TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22591	67996;67997;67998	chr2:178579259;178579258;178579257	chr2:179443986;179443985;179443984
N2AB	20950	63073;63074;63075	chr2:178579259;178579258;178579257	chr2:179443986;179443985;179443984
N2A	20023	60292;60293;60294	chr2:178579259;178579258;178579257	chr2:179443986;179443985;179443984
N2B	13526	40801;40802;40803	chr2:178579259;178579258;178579257	chr2:179443986;179443985;179443984
Novex-1	13651	41176;41177;41178	chr2:178579259;178579258;178579257	chr2:179443986;179443985;179443984
Novex-2	13718	41377;41378;41379	chr2:178579259;178579258;178579257	chr2:179443986;179443985;179443984
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-127
• Domain position: 32
• Structural Position: 58
• Q(SASA): 0.3066
• 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
L/V	None	None	0.026	N	0.383	0.171	0.26169431596	gnomAD-4.0.0	6.84365E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65689E-05

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
L/A	0.4525	ambiguous	0.4558	ambiguous	-2.282	Highly Destabilizing	0.034	N	0.347	neutral	None	None	None	None	N
L/C	0.7294	likely_pathogenic	0.7377	pathogenic	-1.551	Destabilizing	0.997	D	0.572	neutral	None	None	None	None	N
L/D	0.9425	likely_pathogenic	0.9483	pathogenic	-2.39	Highly Destabilizing	0.976	D	0.703	prob.neutral	None	None	None	None	N
L/E	0.7834	likely_pathogenic	0.8008	pathogenic	-2.205	Highly Destabilizing	0.976	D	0.683	prob.neutral	None	None	None	None	N
L/F	0.2912	likely_benign	0.2523	benign	-1.388	Destabilizing	0.988	D	0.459	neutral	None	None	None	None	N
L/G	0.8447	likely_pathogenic	0.8518	pathogenic	-2.782	Highly Destabilizing	0.952	D	0.645	neutral	None	None	None	None	N
L/H	0.7034	likely_pathogenic	0.7001	pathogenic	-2.165	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
L/I	0.1024	likely_benign	0.1	benign	-0.869	Destabilizing	0.811	D	0.47	neutral	N	0.514052496	None	None	N
L/K	0.7476	likely_pathogenic	0.7519	pathogenic	-1.854	Destabilizing	0.976	D	0.601	neutral	None	None	None	None	N
L/M	0.1933	likely_benign	0.184	benign	-0.751	Destabilizing	0.988	D	0.509	neutral	None	None	None	None	N
L/N	0.831	likely_pathogenic	0.836	pathogenic	-2.05	Highly Destabilizing	0.976	D	0.712	prob.delet.	None	None	None	None	N
L/P	0.5839	likely_pathogenic	0.5933	pathogenic	-1.317	Destabilizing	0.984	D	0.707	prob.neutral	D	0.544664627	None	None	N
L/Q	0.5983	likely_pathogenic	0.5981	pathogenic	-1.969	Destabilizing	0.984	D	0.667	neutral	D	0.526813862	None	None	N
L/R	0.6785	likely_pathogenic	0.6788	pathogenic	-1.529	Destabilizing	0.984	D	0.647	neutral	D	0.533308322	None	None	N
L/S	0.6983	likely_pathogenic	0.7126	pathogenic	-2.707	Highly Destabilizing	0.851	D	0.551	neutral	None	None	None	None	N
L/T	0.4881	ambiguous	0.4861	ambiguous	-2.375	Highly Destabilizing	0.261	N	0.359	neutral	None	None	None	None	N
L/V	0.0972	likely_benign	0.0987	benign	-1.317	Destabilizing	0.026	N	0.383	neutral	N	0.519479745	None	None	N
L/W	0.6504	likely_pathogenic	0.6205	pathogenic	-1.7	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
L/Y	0.7105	likely_pathogenic	0.674	pathogenic	-1.405	Destabilizing	0.996	D	0.583	neutral	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.