TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17708	53347;53348;53349	chr2:178607566;178607565;178607564	chr2:179472293;179472292;179472291
N2AB	16067	48424;48425;48426	chr2:178607566;178607565;178607564	chr2:179472293;179472292;179472291
N2A	15140	45643;45644;45645	chr2:178607566;178607565;178607564	chr2:179472293;179472292;179472291
N2B	8643	26152;26153;26154	chr2:178607566;178607565;178607564	chr2:179472293;179472292;179472291
Novex-1	8768	26527;26528;26529	chr2:178607566;178607565;178607564	chr2:179472293;179472292;179472291
Novex-2	8835	26728;26729;26730	chr2:178607566;178607565;178607564	chr2:179472293;179472292;179472291
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-113
• Domain position: 32
• Structural Position: 50
• Q(SASA): 0.2497
• 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/E	rs185913848	0.502	0.106	D	0.378	0.213	None	gnomAD-2.1.1	3.72269E-04	None	None	None	None	N	None	1.65508E-04	4.80824E-04	None	0	0	None	1.96091E-04	None	4E-05	5.73431E-04	4.21585E-04
K/E	rs185913848	0.502	0.106	D	0.378	0.213	None	gnomAD-3.1.2	4.27682E-04	None	None	None	None	N	None	1.20685E-04	2.62329E-04	0	0	0	None	0	0	8.09633E-04	0	4.78469E-04
K/E	rs185913848	0.502	0.106	D	0.378	0.213	None	1000 genomes	7.98722E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	3E-03	None	None	None	0	None
K/E	rs185913848	0.502	0.106	D	0.378	0.213	None	gnomAD-4.0.0	7.12853E-04	None	None	None	None	N	None	1.06695E-04	5.16822E-04	None	0	0	None	0	0	8.96221E-04	3.40383E-04	3.68342E-04
K/I	rs2303832	0.256	None	N	0.349	0.14	None	gnomAD-2.1.1	2.86276E-02	None	None	None	None	N	None	4.96524E-03	3.352E-02	None	1.47173E-02	1.01674E-01	None	6.50412E-03	None	4.8133E-02	2.32443E-02	2.78324E-02
K/I	rs2303832	0.256	None	N	0.349	0.14	None	gnomAD-3.1.2	2.13591E-02	None	None	None	None	N	None	4.61174E-03	2.31719E-02	3.07018E-02	1.90092E-02	9.42623E-02	None	4.48464E-02	6.32911E-03	2.29983E-02	8.07453E-03	2.15311E-02
K/I	rs2303832	0.256	None	N	0.349	0.14	None	1000 genomes	2.95527E-02	None	None	None	None	N	None	8E-04	2.45E-02	None	None	9.92E-02	2.39E-02	None	None	None	6.1E-03	None
K/I	rs2303832	0.256	None	N	0.349	0.14	None	gnomAD-4.0.0	2.35557E-02	None	None	None	None	N	None	4.402E-03	2.98493E-02	None	1.48669E-02	9.23238E-02	None	4.83014E-02	1.00793E-02	2.20499E-02	7.17047E-03	2.34778E-02

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	0.3927	ambiguous	0.4688	ambiguous	-0.936	Destabilizing	0.016	N	0.36	neutral	None	None	None	None	N
K/C	0.5993	likely_pathogenic	0.6148	pathogenic	-0.976	Destabilizing	0.864	D	0.521	neutral	None	None	None	None	N
K/D	0.8796	likely_pathogenic	0.9062	pathogenic	-0.053	Destabilizing	0.136	N	0.573	neutral	None	None	None	None	N
K/E	0.3771	ambiguous	0.4321	ambiguous	0.084	Stabilizing	0.106	N	0.378	neutral	D	0.523360464	None	None	N
K/F	0.6338	likely_pathogenic	0.7537	pathogenic	-0.717	Destabilizing	0.072	N	0.573	neutral	None	None	None	None	N
K/G	0.7042	likely_pathogenic	0.7513	pathogenic	-1.305	Destabilizing	0.136	N	0.505	neutral	None	None	None	None	N
K/H	0.4677	ambiguous	0.5282	ambiguous	-1.611	Destabilizing	0.864	D	0.535	neutral	None	None	None	None	N
K/I	0.0967	likely_benign	0.1168	benign	0.03	Stabilizing	None	N	0.349	neutral	N	0.510572127	None	None	N
K/L	0.188	likely_benign	0.2518	benign	0.03	Stabilizing	None	N	0.327	neutral	None	None	None	None	N
K/M	0.1327	likely_benign	0.1723	benign	-0.054	Destabilizing	0.002	N	0.295	neutral	None	None	None	None	N
K/N	0.6824	likely_pathogenic	0.759	pathogenic	-0.566	Destabilizing	0.295	N	0.472	neutral	N	0.502369373	None	None	N
K/P	0.8524	likely_pathogenic	0.9034	pathogenic	-0.264	Destabilizing	0.628	D	0.574	neutral	None	None	None	None	N
K/Q	0.2271	likely_benign	0.2523	benign	-0.632	Destabilizing	0.295	N	0.471	neutral	N	0.511079106	None	None	N
K/R	0.0907	likely_benign	0.0884	benign	-0.554	Destabilizing	0.055	N	0.425	neutral	N	0.457470222	None	None	N
K/S	0.6429	likely_pathogenic	0.7169	pathogenic	-1.374	Destabilizing	0.072	N	0.375	neutral	None	None	None	None	N
K/T	0.2244	likely_benign	0.2933	benign	-1.01	Destabilizing	0.055	N	0.457	neutral	N	0.516105535	None	None	N
K/V	0.1178	likely_benign	0.1574	benign	-0.264	Destabilizing	None	N	0.322	neutral	None	None	None	None	N
K/W	0.7588	likely_pathogenic	0.8132	pathogenic	-0.515	Destabilizing	0.864	D	0.545	neutral	None	None	None	None	N
K/Y	0.6276	likely_pathogenic	0.7203	pathogenic	-0.205	Destabilizing	0.356	N	0.551	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.