TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3380	10363;10364;10365	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874
N2AB	3380	10363;10364;10365	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874
N2A	3380	10363;10364;10365	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874
N2B	3334	10225;10226;10227	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874
Novex-1	3334	10225;10226;10227	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874
Novex-2	3334	10225;10226;10227	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874
Novex-3	3380	10363;10364;10365	chr2:178759149;178759148;178759147	chr2:179623876;179623875;179623874

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-24
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.6266
• 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
K/R	rs984535715	0.314	0.014	N	0.344	0.108	0.288352970974	gnomAD-2.1.1	4E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/R	rs984535715	0.314	0.014	N	0.344	0.108	0.288352970974	gnomAD-4.0.0	9.57781E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25908E-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
K/A	0.3865	ambiguous	0.4625	ambiguous	-0.295	Destabilizing	0.86	D	0.596	neutral	None	None	None	None	N
K/C	0.8224	likely_pathogenic	0.8056	pathogenic	-0.276	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
K/D	0.5455	ambiguous	0.6252	pathogenic	0.417	Stabilizing	0.915	D	0.545	neutral	None	None	None	None	N
K/E	0.1792	likely_benign	0.2092	benign	0.452	Stabilizing	0.822	D	0.573	neutral	N	0.471412813	None	None	N
K/F	0.8748	likely_pathogenic	0.9019	pathogenic	-0.409	Destabilizing	0.998	D	0.658	neutral	None	None	None	None	N
K/G	0.3385	likely_benign	0.3719	ambiguous	-0.546	Destabilizing	0.86	D	0.571	neutral	None	None	None	None	N
K/H	0.4238	ambiguous	0.44	ambiguous	-0.989	Destabilizing	0.978	D	0.563	neutral	None	None	None	None	N
K/I	0.6188	likely_pathogenic	0.7082	pathogenic	0.303	Stabilizing	0.971	D	0.667	neutral	D	0.616884908	None	None	N
K/L	0.5034	ambiguous	0.5742	pathogenic	0.303	Stabilizing	0.956	D	0.517	neutral	None	None	None	None	N
K/M	0.3858	ambiguous	0.4225	ambiguous	0.283	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
K/N	0.4113	ambiguous	0.4801	ambiguous	0.208	Stabilizing	0.126	N	0.34	neutral	N	0.419768235	None	None	N
K/P	0.7354	likely_pathogenic	0.871	pathogenic	0.133	Stabilizing	0.978	D	0.579	neutral	None	None	None	None	N
K/Q	0.1627	likely_benign	0.1694	benign	0.01	Stabilizing	0.942	D	0.558	neutral	N	0.505917299	None	None	N
K/R	0.0883	likely_benign	0.0843	benign	-0.163	Destabilizing	0.014	N	0.344	neutral	N	0.518396224	None	None	N
K/S	0.4264	ambiguous	0.5064	ambiguous	-0.465	Destabilizing	0.86	D	0.56	neutral	None	None	None	None	N
K/T	0.2947	likely_benign	0.373	ambiguous	-0.256	Destabilizing	0.822	D	0.554	neutral	N	0.517421307	None	None	N
K/V	0.549	ambiguous	0.6306	pathogenic	0.133	Stabilizing	0.956	D	0.609	neutral	None	None	None	None	N
K/W	0.8367	likely_pathogenic	0.8487	pathogenic	-0.304	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
K/Y	0.7578	likely_pathogenic	0.7919	pathogenic	0.034	Stabilizing	0.993	D	0.615	neutral	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.