TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9165	27718;27719;27720	chr2:178712429;178712428;178712427	chr2:179577156;179577155;179577154
N2AB	8848	26767;26768;26769	chr2:178712429;178712428;178712427	chr2:179577156;179577155;179577154
N2A	7921	23986;23987;23988	chr2:178712429;178712428;178712427	chr2:179577156;179577155;179577154
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-77
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3767
• 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	0.001	N	0.145	0.086	0.0611884634855	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.2593	likely_benign	0.299	benign	-0.242	Destabilizing	0.016	N	0.351	neutral	None	None	None	None	N
K/C	0.6796	likely_pathogenic	0.6923	pathogenic	-0.367	Destabilizing	0.864	D	0.488	neutral	None	None	None	None	N
K/D	0.3526	ambiguous	0.4204	ambiguous	0.338	Stabilizing	0.038	N	0.366	neutral	None	None	None	None	N
K/E	0.1454	likely_benign	0.1644	benign	0.387	Stabilizing	0.012	N	0.276	neutral	N	0.504390076	None	None	N
K/F	0.6104	likely_pathogenic	0.6613	pathogenic	-0.259	Destabilizing	0.356	N	0.511	neutral	None	None	None	None	N
K/G	0.3286	likely_benign	0.3596	ambiguous	-0.506	Destabilizing	0.031	N	0.431	neutral	None	None	None	None	N
K/H	0.2368	likely_benign	0.2432	benign	-0.794	Destabilizing	0.356	N	0.441	neutral	None	None	None	None	N
K/I	0.2955	likely_benign	0.3538	ambiguous	0.391	Stabilizing	0.171	N	0.513	neutral	N	0.508231264	None	None	N
K/L	0.2856	likely_benign	0.3268	benign	0.391	Stabilizing	0.038	N	0.437	neutral	None	None	None	None	N
K/M	0.1612	likely_benign	0.1814	benign	0.173	Stabilizing	0.628	D	0.439	neutral	None	None	None	None	N
K/N	0.1922	likely_benign	0.2206	benign	0.022	Stabilizing	0.001	N	0.145	neutral	N	0.438301157	None	None	N
K/P	0.8218	likely_pathogenic	0.8554	pathogenic	0.21	Stabilizing	0.136	N	0.441	neutral	None	None	None	None	N
K/Q	0.1152	likely_benign	0.1169	benign	-0.097	Destabilizing	0.055	N	0.379	neutral	N	0.508046456	None	None	N
K/R	0.0841	likely_benign	0.0842	benign	-0.195	Destabilizing	None	N	0.197	neutral	N	0.500216407	None	None	N
K/S	0.2438	likely_benign	0.2858	benign	-0.594	Destabilizing	0.001	N	0.113	neutral	None	None	None	None	N
K/T	0.0964	likely_benign	0.1141	benign	-0.366	Destabilizing	None	N	0.205	neutral	N	0.473011163	None	None	N
K/V	0.2948	likely_benign	0.3544	ambiguous	0.21	Stabilizing	0.038	N	0.47	neutral	None	None	None	None	N
K/W	0.6887	likely_pathogenic	0.7095	pathogenic	-0.195	Destabilizing	0.864	D	0.526	neutral	None	None	None	None	N
K/Y	0.4321	ambiguous	0.4687	ambiguous	0.131	Stabilizing	0.356	N	0.489	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.