TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6260	19003;19004;19005	chr2:178729378;178729377;178729376	chr2:179594105;179594104;179594103
N2AB	5943	18052;18053;18054	chr2:178729378;178729377;178729376	chr2:179594105;179594104;179594103
N2A	5016	15271;15272;15273	chr2:178729378;178729377;178729376	chr2:179594105;179594104;179594103
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-46
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.4766
• 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/N	None	None	0.004	N	0.29	0.054	0.0482279557977	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	0	None	0	0	0	0	0
K/Q	rs375652574	-0.147	0.638	N	0.462	0.132	None	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	4.71E-05	0
K/Q	rs375652574	-0.147	0.638	N	0.462	0.132	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.0295E-04	0	0
K/Q	rs375652574	-0.147	0.638	N	0.462	0.132	None	gnomAD-4.0.0	5.70167E-05	None	None	None	None	N	None	0	1.6675E-05	None	0	0	None	0	0	7.71422E-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	0.1865	likely_benign	0.2127	benign	-0.206	Destabilizing	0.399	N	0.459	neutral	None	None	None	None	N
K/C	0.5991	likely_pathogenic	0.6158	pathogenic	-0.195	Destabilizing	0.982	D	0.723	prob.delet.	None	None	None	None	N
K/D	0.3031	likely_benign	0.3533	ambiguous	0.146	Stabilizing	0.539	D	0.457	neutral	None	None	None	None	N
K/E	0.1359	likely_benign	0.1594	benign	0.176	Stabilizing	0.201	N	0.458	neutral	N	0.469137699	None	None	N
K/F	0.6545	likely_pathogenic	0.6541	pathogenic	-0.321	Destabilizing	0.947	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.2212	likely_benign	0.2438	benign	-0.459	Destabilizing	0.25	N	0.491	neutral	None	None	None	None	N
K/H	0.2117	likely_benign	0.217	benign	-0.84	Destabilizing	0.826	D	0.525	neutral	None	None	None	None	N
K/I	0.3995	ambiguous	0.4062	ambiguous	0.394	Stabilizing	0.826	D	0.717	prob.delet.	None	None	None	None	N
K/L	0.3267	likely_benign	0.3294	benign	0.394	Stabilizing	0.7	D	0.494	neutral	None	None	None	None	N
K/M	0.2198	likely_benign	0.2356	benign	0.354	Stabilizing	0.976	D	0.508	neutral	N	0.477799295	None	None	N
K/N	0.1938	likely_benign	0.2285	benign	0.152	Stabilizing	0.004	N	0.29	neutral	N	0.453626742	None	None	N
K/P	0.7015	likely_pathogenic	0.6779	pathogenic	0.223	Stabilizing	0.826	D	0.535	neutral	None	None	None	None	N
K/Q	0.105	likely_benign	0.1121	benign	-0.037	Destabilizing	0.638	D	0.462	neutral	N	0.485531303	None	None	N
K/R	0.0718	likely_benign	0.0707	benign	-0.124	Destabilizing	0.002	N	0.331	neutral	N	0.455285754	None	None	N
K/S	0.2115	likely_benign	0.235	benign	-0.438	Destabilizing	0.25	N	0.435	neutral	None	None	None	None	N
K/T	0.1461	likely_benign	0.153	benign	-0.236	Destabilizing	0.334	N	0.465	neutral	N	0.487320815	None	None	N
K/V	0.3166	likely_benign	0.3259	benign	0.223	Stabilizing	0.7	D	0.634	neutral	None	None	None	None	N
K/W	0.6764	likely_pathogenic	0.6637	pathogenic	-0.258	Destabilizing	0.982	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.4513	ambiguous	0.4604	ambiguous	0.081	Stabilizing	0.826	D	0.656	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.