TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22319	67180;67181;67182	chr2:178580424;178580423;178580422	chr2:179445151;179445150;179445149
N2AB	20678	62257;62258;62259	chr2:178580424;178580423;178580422	chr2:179445151;179445150;179445149
N2A	19751	59476;59477;59478	chr2:178580424;178580423;178580422	chr2:179445151;179445150;179445149
N2B	13254	39985;39986;39987	chr2:178580424;178580423;178580422	chr2:179445151;179445150;179445149
Novex-1	13379	40360;40361;40362	chr2:178580424;178580423;178580422	chr2:179445151;179445150;179445149
Novex-2	13446	40561;40562;40563	chr2:178580424;178580423;178580422	chr2:179445151;179445150;179445149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-126
• Domain position: 55
• Structural Position: 138
• Q(SASA): 0.096
• 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	0.999	N	0.655	0.592	0.657603740773	gnomAD-4.0.0	1.59248E-06	None	None	None	None	N	None	0	2.28718E-05	None	0	0	None	0	0	0	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	0.9299	likely_pathogenic	0.9399	pathogenic	-2.885	Highly Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
L/C	0.8837	likely_pathogenic	0.8997	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9995	pathogenic	-3.679	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.9949	likely_pathogenic	0.9952	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/F	0.5353	ambiguous	0.5887	pathogenic	-1.779	Destabilizing	1.0	D	0.816	deleterious	N	0.497998411	None	None	N
L/G	0.9902	likely_pathogenic	0.9917	pathogenic	-3.479	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/H	0.9857	likely_pathogenic	0.9869	pathogenic	-3.128	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/I	0.2166	likely_benign	0.2175	benign	-1.083	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
L/K	0.9922	likely_pathogenic	0.9923	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/M	0.3392	likely_benign	0.3551	ambiguous	-1.189	Destabilizing	1.0	D	0.787	deleterious	D	0.553311908	None	None	N
L/N	0.997	likely_pathogenic	0.9969	pathogenic	-3.052	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/P	0.9969	likely_pathogenic	0.9967	pathogenic	-1.677	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/Q	0.974	likely_pathogenic	0.975	pathogenic	-2.718	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/R	0.9847	likely_pathogenic	0.9851	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/S	0.9904	likely_pathogenic	0.9916	pathogenic	-3.591	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.554832845	None	None	N
L/T	0.973	likely_pathogenic	0.9749	pathogenic	-3.112	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.2452	likely_benign	0.2461	benign	-1.677	Destabilizing	0.999	D	0.655	neutral	N	0.500720663	None	None	N
L/W	0.9455	likely_pathogenic	0.9527	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.554832845	None	None	N
L/Y	0.9501	likely_pathogenic	0.9576	pathogenic	-1.993	Destabilizing	1.0	D	0.859	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.