TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23955	72088;72089;72090	chr2:178574269;178574268;178574267	chr2:179438996;179438995;179438994
N2AB	22314	67165;67166;67167	chr2:178574269;178574268;178574267	chr2:179438996;179438995;179438994
N2A	21387	64384;64385;64386	chr2:178574269;178574268;178574267	chr2:179438996;179438995;179438994
N2B	14890	44893;44894;44895	chr2:178574269;178574268;178574267	chr2:179438996;179438995;179438994
Novex-1	15015	45268;45269;45270	chr2:178574269;178574268;178574267	chr2:179438996;179438995;179438994
Novex-2	15082	45469;45470;45471	chr2:178574269;178574268;178574267	chr2:179438996;179438995;179438994
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: Fn3-62
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5912
• 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	0.961	N	0.635	0.146	0.136095386433	gnomAD-4.0.0	6.84658E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00003E-07	0	0
K/Q	None	None	0.994	N	0.633	0.255	0.180583059064	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3549	ambiguous	0.4074	ambiguous	-0.207	Destabilizing	0.871	D	0.601	neutral	None	None	None	None	N
K/C	0.7211	likely_pathogenic	0.7447	pathogenic	-0.303	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.6559	likely_pathogenic	0.7083	pathogenic	0.206	Stabilizing	0.97	D	0.677	prob.neutral	None	None	None	None	N
K/E	0.2581	likely_benign	0.3251	benign	0.246	Stabilizing	0.961	D	0.62	neutral	N	0.477042319	None	None	N
K/F	0.8237	likely_pathogenic	0.8558	pathogenic	-0.245	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.5436	ambiguous	0.5967	pathogenic	-0.463	Destabilizing	0.97	D	0.635	neutral	None	None	None	None	N
K/H	0.3173	likely_benign	0.3347	benign	-0.724	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/I	0.3993	ambiguous	0.4397	ambiguous	0.403	Stabilizing	0.994	D	0.727	prob.delet.	N	0.465313673	None	None	N
K/L	0.3937	ambiguous	0.4517	ambiguous	0.403	Stabilizing	0.985	D	0.654	neutral	None	None	None	None	N
K/M	0.2851	likely_benign	0.3286	benign	0.212	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/N	0.4848	ambiguous	0.5418	ambiguous	0.062	Stabilizing	0.961	D	0.635	neutral	N	0.449118294	None	None	N
K/P	0.4037	ambiguous	0.456	ambiguous	0.229	Stabilizing	0.996	D	0.632	neutral	None	None	None	None	N
K/Q	0.1327	likely_benign	0.1531	benign	-0.079	Destabilizing	0.994	D	0.633	neutral	N	0.449625273	None	None	N
K/R	0.0788	likely_benign	0.08	benign	-0.156	Destabilizing	0.98	D	0.58	neutral	N	0.464691884	None	None	N
K/S	0.4241	ambiguous	0.4946	ambiguous	-0.525	Destabilizing	0.348	N	0.16	neutral	None	None	None	None	N
K/T	0.2149	likely_benign	0.2569	benign	-0.312	Destabilizing	0.925	D	0.672	neutral	N	0.492243845	None	None	N
K/V	0.357	ambiguous	0.396	ambiguous	0.229	Stabilizing	0.996	D	0.597	neutral	None	None	None	None	N
K/W	0.818	likely_pathogenic	0.8492	pathogenic	-0.19	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/Y	0.6902	likely_pathogenic	0.7233	pathogenic	0.133	Stabilizing	0.999	D	0.715	prob.delet.	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.