TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24087	72484;72485;72486	chr2:178573873;178573872;178573871	chr2:179438600;179438599;179438598
N2AB	22446	67561;67562;67563	chr2:178573873;178573872;178573871	chr2:179438600;179438599;179438598
N2A	21519	64780;64781;64782	chr2:178573873;178573872;178573871	chr2:179438600;179438599;179438598
N2B	15022	45289;45290;45291	chr2:178573873;178573872;178573871	chr2:179438600;179438599;179438598
Novex-1	15147	45664;45665;45666	chr2:178573873;178573872;178573871	chr2:179438600;179438599;179438598
Novex-2	15214	45865;45866;45867	chr2:178573873;178573872;178573871	chr2:179438600;179438599;179438598
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-131
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0781
• 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/P	rs1371976311	-1.715	0.997	D	0.888	0.861	0.90969009521	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	1.12082E-04	None	0	None	0	0	0
L/P	rs1371976311	-1.715	0.997	D	0.888	0.861	0.90969009521	gnomAD-4.0.0	2.74285E-06	None	None	None	None	N	None	0	0	None	0	7.59071E-05	None	0	0	0	0	1.66085E-05
L/V	None	None	0.17	N	0.407	0.427	0.503124787307	gnomAD-4.0.0	1.59748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87318E-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
L/A	0.7465	likely_pathogenic	0.7633	pathogenic	-2.454	Highly Destabilizing	0.953	D	0.705	prob.neutral	None	None	None	None	N
L/C	0.823	likely_pathogenic	0.8179	pathogenic	-1.714	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9986	pathogenic	-3.152	Highly Destabilizing	0.998	D	0.888	deleterious	None	None	None	None	N
L/E	0.9909	likely_pathogenic	0.9898	pathogenic	-2.848	Highly Destabilizing	0.998	D	0.884	deleterious	None	None	None	None	N
L/F	0.4469	ambiguous	0.4602	ambiguous	-1.499	Destabilizing	0.986	D	0.711	prob.delet.	None	None	None	None	N
L/G	0.9766	likely_pathogenic	0.9768	pathogenic	-2.999	Highly Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
L/H	0.9714	likely_pathogenic	0.9717	pathogenic	-2.862	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
L/I	0.1061	likely_benign	0.1038	benign	-0.792	Destabilizing	0.06	N	0.409	neutral	None	None	None	None	N
L/K	0.9843	likely_pathogenic	0.9817	pathogenic	-1.868	Destabilizing	0.993	D	0.862	deleterious	None	None	None	None	N
L/M	0.2297	likely_benign	0.2319	benign	-1.143	Destabilizing	0.982	D	0.693	prob.neutral	D	0.530270128	None	None	N
L/N	0.9931	likely_pathogenic	0.9925	pathogenic	-2.621	Highly Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
L/P	0.9938	likely_pathogenic	0.9927	pathogenic	-1.342	Destabilizing	0.997	D	0.888	deleterious	D	0.567999576	None	None	N
L/Q	0.9652	likely_pathogenic	0.9611	pathogenic	-2.217	Highly Destabilizing	0.997	D	0.873	deleterious	D	0.567999576	None	None	N
L/R	0.9627	likely_pathogenic	0.9598	pathogenic	-2.134	Highly Destabilizing	0.997	D	0.873	deleterious	D	0.579520465	None	None	N
L/S	0.9755	likely_pathogenic	0.977	pathogenic	-3.013	Highly Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	N
L/T	0.8739	likely_pathogenic	0.8741	pathogenic	-2.553	Highly Destabilizing	0.986	D	0.777	deleterious	None	None	None	None	N
L/V	0.1229	likely_benign	0.1258	benign	-1.342	Destabilizing	0.17	N	0.407	neutral	N	0.516191571	None	None	N
L/W	0.9142	likely_pathogenic	0.9212	pathogenic	-1.797	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
L/Y	0.9062	likely_pathogenic	0.9117	pathogenic	-1.686	Destabilizing	0.998	D	0.769	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.