TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19442	58549;58550;58551	chr2:178594069;178594068;178594067	chr2:179458796;179458795;179458794
N2AB	17801	53626;53627;53628	chr2:178594069;178594068;178594067	chr2:179458796;179458795;179458794
N2A	16874	50845;50846;50847	chr2:178594069;178594068;178594067	chr2:179458796;179458795;179458794
N2B	10377	31354;31355;31356	chr2:178594069;178594068;178594067	chr2:179458796;179458795;179458794
Novex-1	10502	31729;31730;31731	chr2:178594069;178594068;178594067	chr2:179458796;179458795;179458794
Novex-2	10569	31930;31931;31932	chr2:178594069;178594068;178594067	chr2:179458796;179458795;179458794
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-118
• Domain position: 52
• Structural Position: 136
• Q(SASA): 0.2604
• 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	rs755527935	-1.178	0.916	N	0.831	0.324	0.422160833541	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/P	rs755527935	-1.178	0.916	N	0.831	0.324	0.422160833541	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
L/R	None	None	0.781	N	0.829	0.301	0.36036328697	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-06	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	0.6116	likely_pathogenic	0.6024	pathogenic	-2.287	Highly Destabilizing	0.399	N	0.66	neutral	None	None	None	None	N
L/C	0.7025	likely_pathogenic	0.7132	pathogenic	-1.711	Destabilizing	0.982	D	0.761	deleterious	None	None	None	None	N
L/D	0.9937	likely_pathogenic	0.9946	pathogenic	-2.471	Highly Destabilizing	0.826	D	0.833	deleterious	None	None	None	None	N
L/E	0.973	likely_pathogenic	0.9786	pathogenic	-2.236	Highly Destabilizing	0.826	D	0.833	deleterious	None	None	None	None	N
L/F	0.3027	likely_benign	0.3363	benign	-1.416	Destabilizing	0.004	N	0.502	neutral	N	0.508213375	None	None	N
L/G	0.9341	likely_pathogenic	0.9336	pathogenic	-2.853	Highly Destabilizing	0.826	D	0.813	deleterious	None	None	None	None	N
L/H	0.9114	likely_pathogenic	0.9232	pathogenic	-2.426	Highly Destabilizing	0.976	D	0.829	deleterious	N	0.473370083	None	None	N
L/I	0.1497	likely_benign	0.1429	benign	-0.652	Destabilizing	0.004	N	0.463	neutral	N	0.501095402	None	None	N
L/K	0.9707	likely_pathogenic	0.9758	pathogenic	-1.552	Destabilizing	0.826	D	0.813	deleterious	None	None	None	None	N
L/M	0.1319	likely_benign	0.1476	benign	-0.688	Destabilizing	0.7	D	0.769	deleterious	None	None	None	None	N
L/N	0.9594	likely_pathogenic	0.96	pathogenic	-1.908	Destabilizing	0.935	D	0.833	deleterious	None	None	None	None	N
L/P	0.9836	likely_pathogenic	0.9855	pathogenic	-1.177	Destabilizing	0.916	D	0.831	deleterious	N	0.455047004	None	None	N
L/Q	0.8986	likely_pathogenic	0.9179	pathogenic	-1.737	Destabilizing	0.982	D	0.825	deleterious	None	None	None	None	N
L/R	0.9521	likely_pathogenic	0.959	pathogenic	-1.419	Destabilizing	0.781	D	0.829	deleterious	N	0.500922043	None	None	N
L/S	0.8306	likely_pathogenic	0.8216	pathogenic	-2.646	Highly Destabilizing	0.826	D	0.799	deleterious	None	None	None	None	N
L/T	0.5475	ambiguous	0.5058	ambiguous	-2.251	Highly Destabilizing	0.7	D	0.691	prob.neutral	None	None	None	None	N
L/V	0.1189	likely_benign	0.1142	benign	-1.177	Destabilizing	0.034	N	0.648	neutral	N	0.464499883	None	None	N
L/W	0.8446	likely_pathogenic	0.8761	pathogenic	-1.811	Destabilizing	0.982	D	0.837	deleterious	None	None	None	None	N
L/Y	0.8695	likely_pathogenic	0.8925	pathogenic	-1.482	Destabilizing	0.539	D	0.767	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.