TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24084	72475;72476;72477	chr2:178573882;178573881;178573880	chr2:179438609;179438608;179438607
N2AB	22443	67552;67553;67554	chr2:178573882;178573881;178573880	chr2:179438609;179438608;179438607
N2A	21516	64771;64772;64773	chr2:178573882;178573881;178573880	chr2:179438609;179438608;179438607
N2B	15019	45280;45281;45282	chr2:178573882;178573881;178573880	chr2:179438609;179438608;179438607
Novex-1	15144	45655;45656;45657	chr2:178573882;178573881;178573880	chr2:179438609;179438608;179438607
Novex-2	15211	45856;45857;45858	chr2:178573882;178573881;178573880	chr2:179438609;179438608;179438607
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-131
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.1814
• 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
S/P	None	None	0.996	D	0.563	0.378	0.479133204078	gnomAD-4.0.0	2.74154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60385E-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
S/A	0.0824	likely_benign	0.091	benign	-0.46	Destabilizing	0.906	D	0.463	neutral	N	0.491884925	None	None	N
S/C	0.0968	likely_benign	0.0983	benign	-0.331	Destabilizing	0.999	D	0.509	neutral	N	0.496874959	None	None	N
S/D	0.5226	ambiguous	0.5106	ambiguous	-0.745	Destabilizing	0.969	D	0.483	neutral	None	None	None	None	N
S/E	0.5318	ambiguous	0.4955	ambiguous	-0.776	Destabilizing	0.939	D	0.469	neutral	None	None	None	None	N
S/F	0.1484	likely_benign	0.1663	benign	-0.761	Destabilizing	0.852	D	0.569	neutral	D	0.525325495	None	None	N
S/G	0.1355	likely_benign	0.1334	benign	-0.683	Destabilizing	0.927	D	0.448	neutral	None	None	None	None	N
S/H	0.2588	likely_benign	0.2225	benign	-1.331	Destabilizing	0.02	N	0.258	neutral	None	None	None	None	N
S/I	0.1656	likely_benign	0.1717	benign	0.018	Stabilizing	0.991	D	0.571	neutral	None	None	None	None	N
S/K	0.5588	ambiguous	0.5164	ambiguous	-0.833	Destabilizing	0.969	D	0.483	neutral	None	None	None	None	N
S/L	0.0977	likely_benign	0.1115	benign	0.018	Stabilizing	0.939	D	0.552	neutral	None	None	None	None	N
S/M	0.2017	likely_benign	0.2126	benign	0.415	Stabilizing	0.997	D	0.525	neutral	None	None	None	None	N
S/N	0.1828	likely_benign	0.1718	benign	-0.75	Destabilizing	0.939	D	0.491	neutral	None	None	None	None	N
S/P	0.842	likely_pathogenic	0.8452	pathogenic	-0.108	Destabilizing	0.996	D	0.563	neutral	D	0.531078032	None	None	N
S/Q	0.4136	ambiguous	0.3712	ambiguous	-0.97	Destabilizing	0.991	D	0.529	neutral	None	None	None	None	N
S/R	0.4485	ambiguous	0.4009	ambiguous	-0.659	Destabilizing	0.982	D	0.554	neutral	None	None	None	None	N
S/T	0.0763	likely_benign	0.0795	benign	-0.676	Destabilizing	0.959	D	0.48	neutral	N	0.431663186	None	None	N
S/V	0.1717	likely_benign	0.1815	benign	-0.108	Destabilizing	0.939	D	0.57	neutral	None	None	None	None	N
S/W	0.3068	likely_benign	0.3181	benign	-0.806	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
S/Y	0.1595	likely_benign	0.1649	benign	-0.527	Destabilizing	0.134	N	0.365	neutral	N	0.485113669	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.