TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6242	18949;18950;18951	chr2:178729432;178729431;178729430	chr2:179594159;179594158;179594157
N2AB	5925	17998;17999;18000	chr2:178729432;178729431;178729430	chr2:179594159;179594158;179594157
N2A	4998	15217;15218;15219	chr2:178729432;178729431;178729430	chr2:179594159;179594158;179594157
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-46
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3509
• 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
S/G	None	None	0.001	N	0.237	0.106	0.0806252709748	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.1843	likely_benign	0.199	benign	-0.483	Destabilizing	0.121	N	0.349	neutral	None	None	None	None	N
S/C	0.1889	likely_benign	0.2524	benign	-0.395	Destabilizing	0.976	D	0.42	neutral	N	0.487526667	None	None	N
S/D	0.544	ambiguous	0.6806	pathogenic	0.467	Stabilizing	0.399	N	0.338	neutral	None	None	None	None	N
S/E	0.8201	likely_pathogenic	0.8961	pathogenic	0.389	Stabilizing	0.574	D	0.333	neutral	None	None	None	None	N
S/F	0.6776	likely_pathogenic	0.7024	pathogenic	-1.109	Destabilizing	0.935	D	0.511	neutral	None	None	None	None	N
S/G	0.0609	likely_benign	0.0781	benign	-0.591	Destabilizing	0.001	N	0.237	neutral	N	0.440836377	None	None	N
S/H	0.6289	likely_pathogenic	0.7025	pathogenic	-1.003	Destabilizing	0.982	D	0.377	neutral	None	None	None	None	N
S/I	0.5241	ambiguous	0.613	pathogenic	-0.326	Destabilizing	0.781	D	0.49	neutral	N	0.487273177	None	None	N
S/K	0.9079	likely_pathogenic	0.9479	pathogenic	-0.359	Destabilizing	0.399	N	0.354	neutral	None	None	None	None	N
S/L	0.3255	likely_benign	0.3378	benign	-0.326	Destabilizing	0.826	D	0.433	neutral	None	None	None	None	N
S/M	0.4947	ambiguous	0.5255	ambiguous	-0.213	Destabilizing	0.982	D	0.395	neutral	None	None	None	None	N
S/N	0.2002	likely_benign	0.2635	benign	-0.197	Destabilizing	0.334	N	0.383	neutral	N	0.488630324	None	None	N
S/P	0.8127	likely_pathogenic	0.8235	pathogenic	-0.35	Destabilizing	0.826	D	0.355	neutral	None	None	None	None	N
S/Q	0.775	likely_pathogenic	0.8465	pathogenic	-0.359	Destabilizing	0.826	D	0.325	neutral	None	None	None	None	N
S/R	0.8627	likely_pathogenic	0.9126	pathogenic	-0.212	Destabilizing	0.781	D	0.353	neutral	N	0.466838291	None	None	N
S/T	0.1293	likely_benign	0.1532	benign	-0.311	Destabilizing	0.334	N	0.364	neutral	N	0.50046347	None	None	N
S/V	0.4829	ambiguous	0.5722	pathogenic	-0.35	Destabilizing	0.826	D	0.471	neutral	None	None	None	None	N
S/W	0.7218	likely_pathogenic	0.7487	pathogenic	-1.122	Destabilizing	0.982	D	0.634	neutral	None	None	None	None	N
S/Y	0.567	likely_pathogenic	0.6252	pathogenic	-0.828	Destabilizing	0.935	D	0.504	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.