TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9197	27814;27815;27816	chr2:178712333;178712332;178712331	chr2:179577060;179577059;179577058
N2AB	8880	26863;26864;26865	chr2:178712333;178712332;178712331	chr2:179577060;179577059;179577058
N2A	7953	24082;24083;24084	chr2:178712333;178712332;178712331	chr2:179577060;179577059;179577058
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-77
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1627
• 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
A/V	rs1219833647	-0.401	0.969	N	0.66	0.416	0.59544603514	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
A/V	rs1219833647	-0.401	0.969	N	0.66	0.416	0.59544603514	gnomAD-4.0.0	1.36863E-06	None	None	None	None	N	None	2.98829E-05	0	None	0	2.51927E-05	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
A/C	0.6559	likely_pathogenic	0.6109	pathogenic	-1.596	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
A/D	0.9739	likely_pathogenic	0.9332	pathogenic	-2.244	Highly Destabilizing	0.986	D	0.803	deleterious	None	None	None	None	N
A/E	0.9648	likely_pathogenic	0.916	pathogenic	-2.149	Highly Destabilizing	0.982	D	0.765	deleterious	D	0.544736625	None	None	N
A/F	0.8924	likely_pathogenic	0.7828	pathogenic	-1.083	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
A/G	0.202	likely_benign	0.1606	benign	-1.595	Destabilizing	0.046	N	0.319	neutral	N	0.493057206	None	None	N
A/H	0.9702	likely_pathogenic	0.932	pathogenic	-1.849	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
A/I	0.7151	likely_pathogenic	0.6209	pathogenic	-0.226	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
A/K	0.9872	likely_pathogenic	0.9672	pathogenic	-1.47	Destabilizing	0.986	D	0.765	deleterious	None	None	None	None	N
A/L	0.6827	likely_pathogenic	0.5579	ambiguous	-0.226	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
A/M	0.7208	likely_pathogenic	0.6046	pathogenic	-0.428	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
A/N	0.9186	likely_pathogenic	0.8315	pathogenic	-1.571	Destabilizing	0.986	D	0.828	deleterious	None	None	None	None	N
A/P	0.9807	likely_pathogenic	0.9546	pathogenic	-0.509	Destabilizing	0.991	D	0.808	deleterious	D	0.544990114	None	None	N
A/Q	0.9421	likely_pathogenic	0.8908	pathogenic	-1.571	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	N
A/R	0.9667	likely_pathogenic	0.9276	pathogenic	-1.29	Destabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
A/S	0.1452	likely_benign	0.1196	benign	-1.988	Destabilizing	0.58	D	0.377	neutral	N	0.501171054	None	None	N
A/T	0.2108	likely_benign	0.1665	benign	-1.775	Destabilizing	0.885	D	0.613	neutral	D	0.531792895	None	None	N
A/V	0.381	ambiguous	0.3133	benign	-0.509	Destabilizing	0.969	D	0.66	neutral	N	0.493823539	None	None	N
A/W	0.9906	likely_pathogenic	0.9742	pathogenic	-1.636	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
A/Y	0.9617	likely_pathogenic	0.9078	pathogenic	-1.152	Destabilizing	0.998	D	0.861	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.