TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22608	68047;68048;68049	chr2:178579208;178579207;178579206	chr2:179443935;179443934;179443933
N2AB	20967	63124;63125;63126	chr2:178579208;178579207;178579206	chr2:179443935;179443934;179443933
N2A	20040	60343;60344;60345	chr2:178579208;178579207;178579206	chr2:179443935;179443934;179443933
N2B	13543	40852;40853;40854	chr2:178579208;178579207;178579206	chr2:179443935;179443934;179443933
Novex-1	13668	41227;41228;41229	chr2:178579208;178579207;178579206	chr2:179443935;179443934;179443933
Novex-2	13735	41428;41429;41430	chr2:178579208;178579207;178579206	chr2:179443935;179443934;179443933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-127
• Domain position: 49
• Structural Position: 138
• Q(SASA): 0.1184
• 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/F	rs749645303	-1.491	1.0	N	0.797	0.602	0.82342218508	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02554E-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	0.9543	likely_pathogenic	0.9564	pathogenic	-2.443	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
L/C	0.928	likely_pathogenic	0.9377	pathogenic	-1.567	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.118	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/E	0.9983	likely_pathogenic	0.9982	pathogenic	-2.786	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/F	0.4639	ambiguous	0.4369	ambiguous	-1.497	Destabilizing	1.0	D	0.797	deleterious	N	0.499808837	None	None	N
L/G	0.994	likely_pathogenic	0.9942	pathogenic	-3.041	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/H	0.9897	likely_pathogenic	0.9894	pathogenic	-2.96	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.556807854	None	None	N
L/I	0.2441	likely_benign	0.2227	benign	-0.628	Destabilizing	0.999	D	0.665	neutral	N	0.511467857	None	None	N
L/K	0.9951	likely_pathogenic	0.9943	pathogenic	-1.84	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/M	0.3297	likely_benign	0.3191	benign	-0.858	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/N	0.9984	likely_pathogenic	0.9984	pathogenic	-2.645	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9975	pathogenic	-1.227	Destabilizing	1.0	D	0.833	deleterious	D	0.556807854	None	None	N
L/Q	0.9897	likely_pathogenic	0.9893	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/R	0.9869	likely_pathogenic	0.9853	pathogenic	-2.181	Highly Destabilizing	1.0	D	0.812	deleterious	D	0.556807854	None	None	N
L/S	0.9963	likely_pathogenic	0.9964	pathogenic	-3.085	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/T	0.9872	likely_pathogenic	0.9873	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/V	0.2847	likely_benign	0.2791	benign	-1.227	Destabilizing	0.999	D	0.676	prob.neutral	N	0.515533235	None	None	N
L/W	0.9272	likely_pathogenic	0.9256	pathogenic	-1.815	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/Y	0.9297	likely_pathogenic	0.9297	pathogenic	-1.658	Destabilizing	1.0	D	0.761	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.