TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23103	69532;69533;69534	chr2:178577028;178577027;178577026	chr2:179441755;179441754;179441753
N2AB	21462	64609;64610;64611	chr2:178577028;178577027;178577026	chr2:179441755;179441754;179441753
N2A	20535	61828;61829;61830	chr2:178577028;178577027;178577026	chr2:179441755;179441754;179441753
N2B	14038	42337;42338;42339	chr2:178577028;178577027;178577026	chr2:179441755;179441754;179441753
Novex-1	14163	42712;42713;42714	chr2:178577028;178577027;178577026	chr2:179441755;179441754;179441753
Novex-2	14230	42913;42914;42915	chr2:178577028;178577027;178577026	chr2:179441755;179441754;179441753
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-55
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.9007
• 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	None	None	0.99	N	0.483	0.285	0.21279746466	gnomAD-4.0.0	1.59186E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85966E-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
K/A	0.7896	likely_pathogenic	0.799	pathogenic	0.038	Stabilizing	0.985	D	0.442	neutral	None	None	None	None	N
K/C	0.9054	likely_pathogenic	0.8976	pathogenic	-0.393	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/D	0.8818	likely_pathogenic	0.8975	pathogenic	-0.154	Destabilizing	0.971	D	0.479	neutral	None	None	None	None	N
K/E	0.7445	likely_pathogenic	0.7792	pathogenic	-0.16	Destabilizing	0.98	D	0.475	neutral	N	0.504704215	None	None	N
K/F	0.973	likely_pathogenic	0.9758	pathogenic	-0.241	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
K/G	0.6663	likely_pathogenic	0.6783	pathogenic	-0.112	Destabilizing	0.171	N	0.345	neutral	None	None	None	None	N
K/H	0.5077	ambiguous	0.4805	ambiguous	-0.196	Destabilizing	0.999	D	0.479	neutral	None	None	None	None	N
K/I	0.9288	likely_pathogenic	0.9447	pathogenic	0.35	Stabilizing	0.999	D	0.617	neutral	N	0.50185653	None	None	N
K/L	0.839	likely_pathogenic	0.8458	pathogenic	0.35	Stabilizing	0.998	D	0.483	neutral	None	None	None	None	N
K/M	0.7817	likely_pathogenic	0.8035	pathogenic	-0.015	Destabilizing	1.0	D	0.491	neutral	None	None	None	None	N
K/N	0.7775	likely_pathogenic	0.8166	pathogenic	0.081	Stabilizing	0.4	N	0.289	neutral	N	0.478650977	None	None	N
K/P	0.9356	likely_pathogenic	0.9486	pathogenic	0.271	Stabilizing	0.999	D	0.486	neutral	None	None	None	None	N
K/Q	0.4164	ambiguous	0.4197	ambiguous	-0.07	Destabilizing	0.997	D	0.548	neutral	N	0.487257767	None	None	N
K/R	0.099	likely_benign	0.0921	benign	-0.037	Destabilizing	0.99	D	0.483	neutral	N	0.468399485	None	None	N
K/S	0.7929	likely_pathogenic	0.8036	pathogenic	-0.325	Destabilizing	0.985	D	0.461	neutral	None	None	None	None	N
K/T	0.7112	likely_pathogenic	0.7316	pathogenic	-0.205	Destabilizing	0.98	D	0.446	neutral	N	0.487764746	None	None	N
K/V	0.8706	likely_pathogenic	0.8818	pathogenic	0.271	Stabilizing	0.999	D	0.515	neutral	None	None	None	None	N
K/W	0.9511	likely_pathogenic	0.9438	pathogenic	-0.318	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
K/Y	0.9023	likely_pathogenic	0.9021	pathogenic	0.034	Stabilizing	0.999	D	0.567	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.