TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25529	76810;76811;76812	chr2:178569547;178569546;178569545	chr2:179434274;179434273;179434272
N2AB	23888	71887;71888;71889	chr2:178569547;178569546;178569545	chr2:179434274;179434273;179434272
N2A	22961	69106;69107;69108	chr2:178569547;178569546;178569545	chr2:179434274;179434273;179434272
N2B	16464	49615;49616;49617	chr2:178569547;178569546;178569545	chr2:179434274;179434273;179434272
Novex-1	16589	49990;49991;49992	chr2:178569547;178569546;178569545	chr2:179434274;179434273;179434272
Novex-2	16656	50191;50192;50193	chr2:178569547;178569546;178569545	chr2:179434274;179434273;179434272
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-135
• Domain position: 16
• Structural Position: 29
• Q(SASA): 0.7567
• Predicted PPI site: I

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
R/K	rs750282861	0.1	0.014	N	0.312	0.173	0.104622674875	gnomAD-2.1.1	2.42E-05	None	None	None	None	I	None	0	1.74571E-04	None	0	0	None	0	None	0	0	0
R/K	rs750282861	0.1	0.014	N	0.312	0.173	0.104622674875	gnomAD-4.0.0	4.10715E-06	None	None	None	None	I	None	0	1.34391E-04	None	0	0	None	0	0	0	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
R/A	0.9496	likely_pathogenic	0.9639	pathogenic	-0.276	Destabilizing	0.86	D	0.625	neutral	None	None	None	None	I
R/C	0.4738	ambiguous	0.5159	ambiguous	-0.473	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	I
R/D	0.9821	likely_pathogenic	0.9854	pathogenic	-0.008	Destabilizing	0.956	D	0.603	neutral	None	None	None	None	I
R/E	0.8966	likely_pathogenic	0.9175	pathogenic	0.058	Stabilizing	0.754	D	0.643	neutral	None	None	None	None	I
R/F	0.9257	likely_pathogenic	0.9363	pathogenic	-0.507	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	I
R/G	0.9135	likely_pathogenic	0.9339	pathogenic	-0.471	Destabilizing	0.822	D	0.599	neutral	N	0.476607526	None	None	I
R/H	0.2226	likely_benign	0.2581	benign	-0.818	Destabilizing	0.978	D	0.657	neutral	None	None	None	None	I
R/I	0.8055	likely_pathogenic	0.8343	pathogenic	0.204	Stabilizing	0.978	D	0.679	prob.neutral	None	None	None	None	I
R/K	0.34	ambiguous	0.3866	ambiguous	-0.298	Destabilizing	0.014	N	0.312	neutral	N	0.498073739	None	None	I
R/L	0.7605	likely_pathogenic	0.7957	pathogenic	0.204	Stabilizing	0.86	D	0.599	neutral	None	None	None	None	I
R/M	0.8364	likely_pathogenic	0.865	pathogenic	-0.158	Destabilizing	0.992	D	0.661	neutral	N	0.479481135	None	None	I
R/N	0.9497	likely_pathogenic	0.9597	pathogenic	-0.058	Destabilizing	0.86	D	0.611	neutral	None	None	None	None	I
R/P	0.9906	likely_pathogenic	0.9924	pathogenic	0.064	Stabilizing	0.978	D	0.679	prob.neutral	None	None	None	None	I
R/Q	0.3009	likely_benign	0.3503	ambiguous	-0.201	Destabilizing	0.16	N	0.367	neutral	None	None	None	None	I
R/S	0.9348	likely_pathogenic	0.9506	pathogenic	-0.559	Destabilizing	0.822	D	0.615	neutral	N	0.509637527	None	None	I
R/T	0.8339	likely_pathogenic	0.8766	pathogenic	-0.353	Destabilizing	0.822	D	0.599	neutral	N	0.495473364	None	None	I
R/V	0.8435	likely_pathogenic	0.8731	pathogenic	0.064	Stabilizing	0.956	D	0.646	neutral	None	None	None	None	I
R/W	0.5338	ambiguous	0.5477	ambiguous	-0.473	Destabilizing	0.997	D	0.663	neutral	N	0.50648616	None	None	I
R/Y	0.7825	likely_pathogenic	0.803	pathogenic	-0.081	Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	I

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.