TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14935	45028;45029;45030	chr2:178624477;178624476;178624475	chr2:179489204;179489203;179489202
N2AB	13294	40105;40106;40107	chr2:178624477;178624476;178624475	chr2:179489204;179489203;179489202
N2A	12367	37324;37325;37326	chr2:178624477;178624476;178624475	chr2:179489204;179489203;179489202
N2B	5870	17833;17834;17835	chr2:178624477;178624476;178624475	chr2:179489204;179489203;179489202
Novex-1	5995	18208;18209;18210	chr2:178624477;178624476;178624475	chr2:179489204;179489203;179489202
Novex-2	6062	18409;18410;18411	chr2:178624477;178624476;178624475	chr2:179489204;179489203;179489202
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-100
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1179
• 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	rs1230286076	None	0.999	N	0.552	0.22	0.443797312901	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs1230286076	None	0.999	N	0.552	0.22	0.443797312901	gnomAD-4.0.0	6.58172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47202E-05	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	0.9673	likely_pathogenic	0.9748	pathogenic	-2.884	Highly Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
L/C	0.962	likely_pathogenic	0.9696	pathogenic	-2.433	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9995	pathogenic	-3.715	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/E	0.9946	likely_pathogenic	0.9972	pathogenic	-3.475	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/F	0.7531	likely_pathogenic	0.8392	pathogenic	-1.653	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/G	0.9914	likely_pathogenic	0.995	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/H	0.9893	likely_pathogenic	0.9942	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/I	0.2353	likely_benign	0.2441	benign	-1.279	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
L/K	0.987	likely_pathogenic	0.9938	pathogenic	-2.353	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
L/M	0.4564	ambiguous	0.5002	ambiguous	-1.401	Destabilizing	1.0	D	0.747	deleterious	N	0.506403587	None	None	N
L/N	0.9948	likely_pathogenic	0.997	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/P	0.995	likely_pathogenic	0.9973	pathogenic	-1.801	Destabilizing	1.0	D	0.811	deleterious	D	0.564117909	None	None	N
L/Q	0.9807	likely_pathogenic	0.9897	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.81	deleterious	D	0.564117909	None	None	N
L/R	0.9748	likely_pathogenic	0.9868	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.817	deleterious	D	0.563697447	None	None	N
L/S	0.9948	likely_pathogenic	0.9967	pathogenic	-3.432	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/T	0.9682	likely_pathogenic	0.9776	pathogenic	-3.055	Highly Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
L/V	0.3485	ambiguous	0.3338	benign	-1.801	Destabilizing	0.999	D	0.552	neutral	N	0.385283281	None	None	N
L/W	0.9648	likely_pathogenic	0.983	pathogenic	-2.168	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/Y	0.9775	likely_pathogenic	0.9859	pathogenic	-1.965	Destabilizing	1.0	D	0.821	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.