TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1379	4360;4361;4362	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672
N2AB	1379	4360;4361;4362	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672
N2A	1379	4360;4361;4362	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672
N2B	1333	4222;4223;4224	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672
Novex-1	1333	4222;4223;4224	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672
Novex-2	1333	4222;4223;4224	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672
Novex-3	1379	4360;4361;4362	chr2:178778947;178778946;178778945	chr2:179643674;179643673;179643672

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-5
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.0624
• 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	rs1204391475	None	0.999	D	0.596	0.368	0.307332253619	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
L/V	rs1204391475	None	0.999	D	0.596	0.368	0.307332253619	gnomAD-4.0.0	3.84239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.17666E-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	0.9811	likely_pathogenic	0.9854	pathogenic	-2.586	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
L/C	0.9776	likely_pathogenic	0.9824	pathogenic	-1.374	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.189	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.9991	pathogenic	-2.859	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/F	0.9385	likely_pathogenic	0.9626	pathogenic	-1.603	Destabilizing	1.0	D	0.841	deleterious	D	0.676942219	None	None	N
L/G	0.9965	likely_pathogenic	0.9972	pathogenic	-3.181	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/H	0.9985	likely_pathogenic	0.9989	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/I	0.3609	ambiguous	0.4009	ambiguous	-0.78	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
L/K	0.9983	likely_pathogenic	0.9985	pathogenic	-1.84	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/M	0.686	likely_pathogenic	0.7361	pathogenic	-0.867	Destabilizing	1.0	D	0.81	deleterious	D	0.678097715	None	None	N
L/N	0.9987	likely_pathogenic	0.9987	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/P	0.9995	likely_pathogenic	0.9996	pathogenic	-1.376	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/Q	0.9976	likely_pathogenic	0.9983	pathogenic	-2.201	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/R	0.9956	likely_pathogenic	0.9965	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/S	0.9989	likely_pathogenic	0.9991	pathogenic	-3.056	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.774424268	None	None	N
L/T	0.993	likely_pathogenic	0.9938	pathogenic	-2.561	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/V	0.4933	ambiguous	0.5552	ambiguous	-1.376	Destabilizing	0.999	D	0.596	neutral	D	0.536299019	None	None	N
L/W	0.9969	likely_pathogenic	0.9979	pathogenic	-1.948	Destabilizing	1.0	D	0.887	deleterious	D	0.774424268	None	None	N
L/Y	0.994	likely_pathogenic	0.9957	pathogenic	-1.769	Destabilizing	1.0	D	0.889	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.