TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9995	30208;30209;30210	chr2:178704387;178704386;178704385	chr2:179569114;179569113;179569112
N2AB	9678	29257;29258;29259	chr2:178704387;178704386;178704385	chr2:179569114;179569113;179569112
N2A	8751	26476;26477;26478	chr2:178704387;178704386;178704385	chr2:179569114;179569113;179569112
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-85
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1148
• 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/P	rs1060500554	None	0.999	None	0.883	0.437	0.676897640743	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
L/P	rs1060500554	None	0.999	None	0.883	0.437	0.676897640743	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
L/P	rs1060500554	None	0.999	None	0.883	0.437	0.676897640743	gnomAD-4.0.0	6.40658E-06	None	None	None	None	N	None	0	0	None	0	0	None	7.84412E-05	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	0.9562	likely_pathogenic	0.9642	pathogenic	-2.042	Highly Destabilizing	0.967	D	0.542	neutral	None	None	None	None	N
L/C	0.9738	likely_pathogenic	0.9798	pathogenic	-1.342	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9993	pathogenic	-2.205	Highly Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
L/E	0.994	likely_pathogenic	0.9946	pathogenic	-2.184	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
L/F	0.8228	likely_pathogenic	0.8619	pathogenic	-1.55	Destabilizing	0.994	D	0.689	prob.neutral	None	None	None	None	N
L/G	0.9913	likely_pathogenic	0.9927	pathogenic	-2.397	Highly Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	N
L/H	0.9887	likely_pathogenic	0.9901	pathogenic	-1.682	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/I	0.3709	ambiguous	0.418	ambiguous	-1.104	Destabilizing	0.956	D	0.477	neutral	None	None	None	None	N
L/K	0.9894	likely_pathogenic	0.9896	pathogenic	-1.399	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
L/M	0.4022	ambiguous	0.512	ambiguous	-0.827	Destabilizing	0.923	D	0.443	neutral	None	None	None	None	N
L/N	0.9951	likely_pathogenic	0.9956	pathogenic	-1.295	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
L/P	0.9635	likely_pathogenic	0.9743	pathogenic	-1.39	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/Q	0.9705	likely_pathogenic	0.9761	pathogenic	-1.507	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
L/R	0.9799	likely_pathogenic	0.9804	pathogenic	-0.796	Destabilizing	0.997	D	0.837	deleterious	None	None	None	None	N
L/S	0.9907	likely_pathogenic	0.9922	pathogenic	-1.858	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
L/T	0.9649	likely_pathogenic	0.973	pathogenic	-1.725	Destabilizing	0.995	D	0.724	prob.delet.	None	None	None	None	N
L/V	0.4917	ambiguous	0.577	pathogenic	-1.39	Destabilizing	0.37	N	0.359	neutral	None	None	None	None	N
L/W	0.9811	likely_pathogenic	0.9835	pathogenic	-1.697	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/Y	0.9918	likely_pathogenic	0.993	pathogenic	-1.469	Destabilizing	0.999	D	0.81	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.