TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19133	57622;57623;57624	chr2:178597685;178597684;178597683	chr2:179462412;179462411;179462410
N2AB	17492	52699;52700;52701	chr2:178597685;178597684;178597683	chr2:179462412;179462411;179462410
N2A	16565	49918;49919;49920	chr2:178597685;178597684;178597683	chr2:179462412;179462411;179462410
N2B	10068	30427;30428;30429	chr2:178597685;178597684;178597683	chr2:179462412;179462411;179462410
Novex-1	10193	30802;30803;30804	chr2:178597685;178597684;178597683	chr2:179462412;179462411;179462410
Novex-2	10260	31003;31004;31005	chr2:178597685;178597684;178597683	chr2:179462412;179462411;179462410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-117
• Domain position: 39
• Structural Position: 58
• Q(SASA): 0.1689
• 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	rs1576219060	None	0.999	D	0.727	0.459	0.663553952235	gnomAD-4.0.0	3.18431E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-05	3.02572E-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	0.6051	likely_pathogenic	0.6687	pathogenic	-2.202	Highly Destabilizing	0.997	D	0.502	neutral	None	None	None	None	N
L/C	0.8064	likely_pathogenic	0.848	pathogenic	-1.402	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
L/D	0.9836	likely_pathogenic	0.9905	pathogenic	-1.778	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/E	0.9344	likely_pathogenic	0.9579	pathogenic	-1.673	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/F	0.4206	ambiguous	0.5678	pathogenic	-1.488	Destabilizing	0.999	D	0.727	prob.delet.	D	0.535548063	None	None	N
L/G	0.9222	likely_pathogenic	0.9497	pathogenic	-2.631	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/H	0.8777	likely_pathogenic	0.9314	pathogenic	-1.816	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/I	0.1008	likely_benign	0.1177	benign	-1.025	Destabilizing	0.981	D	0.507	neutral	N	0.450483807	None	None	N
L/K	0.8992	likely_pathogenic	0.9271	pathogenic	-1.541	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/M	0.2114	likely_benign	0.2461	benign	-0.837	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
L/N	0.9238	likely_pathogenic	0.947	pathogenic	-1.525	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/P	0.4295	ambiguous	0.5196	ambiguous	-1.391	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/Q	0.8144	likely_pathogenic	0.8805	pathogenic	-1.564	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/R	0.8601	likely_pathogenic	0.9101	pathogenic	-1.074	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/S	0.8546	likely_pathogenic	0.9197	pathogenic	-2.205	Highly Destabilizing	0.999	D	0.772	deleterious	N	0.521280453	None	None	N
L/T	0.6798	likely_pathogenic	0.7544	pathogenic	-1.956	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
L/V	0.1067	likely_benign	0.1243	benign	-1.391	Destabilizing	0.767	D	0.286	neutral	N	0.475574252	None	None	N
L/W	0.796	likely_pathogenic	0.8931	pathogenic	-1.624	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/Y	0.8446	likely_pathogenic	0.9035	pathogenic	-1.396	Destabilizing	1.0	D	0.771	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.