TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22905	68938;68939;68940	chr2:178577713;178577712;178577711	chr2:179442440;179442439;179442438
N2AB	21264	64015;64016;64017	chr2:178577713;178577712;178577711	chr2:179442440;179442439;179442438
N2A	20337	61234;61235;61236	chr2:178577713;178577712;178577711	chr2:179442440;179442439;179442438
N2B	13840	41743;41744;41745	chr2:178577713;178577712;178577711	chr2:179442440;179442439;179442438
Novex-1	13965	42118;42119;42120	chr2:178577713;178577712;178577711	chr2:179442440;179442439;179442438
Novex-2	14032	42319;42320;42321	chr2:178577713;178577712;178577711	chr2:179442440;179442439;179442438
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-54
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.9666
• 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
D/E	None	None	1.0	N	0.453	0.298	0.286465849087	gnomAD-4.0.0	2.05317E-06	None	None	None	None	N	None	2.98882E-05	0	None	0	0	None	0	0	1.79923E-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
D/A	0.282	likely_benign	0.291	benign	0.005	Stabilizing	1.0	D	0.617	neutral	N	0.505069574	None	None	N
D/C	0.7876	likely_pathogenic	0.801	pathogenic	0.088	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
D/E	0.2331	likely_benign	0.2399	benign	-0.222	Destabilizing	1.0	D	0.453	neutral	N	0.476632179	None	None	N
D/F	0.8497	likely_pathogenic	0.856	pathogenic	-0.111	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
D/G	0.1565	likely_benign	0.1563	benign	-0.121	Destabilizing	1.0	D	0.655	neutral	N	0.366285477	None	None	N
D/H	0.4615	ambiguous	0.4845	ambiguous	0.32	Stabilizing	1.0	D	0.62	neutral	N	0.469861074	None	None	N
D/I	0.774	likely_pathogenic	0.7957	pathogenic	0.267	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
D/K	0.628	likely_pathogenic	0.6621	pathogenic	0.526	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	N
D/L	0.6984	likely_pathogenic	0.7034	pathogenic	0.267	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
D/M	0.8362	likely_pathogenic	0.842	pathogenic	0.212	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
D/N	0.1252	likely_benign	0.1223	benign	0.339	Stabilizing	1.0	D	0.648	neutral	N	0.437321643	None	None	N
D/P	0.8834	likely_pathogenic	0.8948	pathogenic	0.2	Stabilizing	1.0	D	0.61	neutral	None	None	None	None	N
D/Q	0.532	ambiguous	0.5542	ambiguous	0.336	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	N
D/R	0.6716	likely_pathogenic	0.7024	pathogenic	0.673	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	N
D/S	0.1665	likely_benign	0.1657	benign	0.238	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
D/T	0.4136	ambiguous	0.425	ambiguous	0.337	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
D/V	0.5709	likely_pathogenic	0.5938	pathogenic	0.2	Stabilizing	1.0	D	0.621	neutral	N	0.511691898	None	None	N
D/W	0.9627	likely_pathogenic	0.9662	pathogenic	-0.07	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
D/Y	0.4771	ambiguous	0.497	ambiguous	0.116	Stabilizing	1.0	D	0.639	neutral	N	0.511691898	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.