TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22984	69175;69176;69177	chr2:178577385;178577384;178577383	chr2:179442112;179442111;179442110
N2AB	21343	64252;64253;64254	chr2:178577385;178577384;178577383	chr2:179442112;179442111;179442110
N2A	20416	61471;61472;61473	chr2:178577385;178577384;178577383	chr2:179442112;179442111;179442110
N2B	13919	41980;41981;41982	chr2:178577385;178577384;178577383	chr2:179442112;179442111;179442110
Novex-1	14044	42355;42356;42357	chr2:178577385;178577384;178577383	chr2:179442112;179442111;179442110
Novex-2	14111	42556;42557;42558	chr2:178577385;178577384;178577383	chr2:179442112;179442111;179442110
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-128
• Domain position: 35
• Structural Position: 51
• Q(SASA): 0.4207
• 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
A/T	None	None	0.505	N	0.422	0.145	0.107399877778	gnomAD-4.0.0	2.05334E-06	None	None	None	None	N	None	0	0	None	0	2.52564E-05	None	0	0	0	2.3197E-05	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
A/C	0.3379	likely_benign	0.3264	benign	-0.77	Destabilizing	0.991	D	0.463	neutral	None	None	None	None	N
A/D	0.1275	likely_benign	0.1054	benign	-0.338	Destabilizing	0.004	N	0.361	neutral	None	None	None	None	N
A/E	0.1681	likely_benign	0.1459	benign	-0.494	Destabilizing	0.007	N	0.284	neutral	N	0.413089628	None	None	N
A/F	0.2412	likely_benign	0.2077	benign	-0.826	Destabilizing	0.967	D	0.629	neutral	None	None	None	None	N
A/G	0.0711	likely_benign	0.0688	benign	-0.163	Destabilizing	0.001	N	0.153	neutral	N	0.391231489	None	None	N
A/H	0.3641	ambiguous	0.3127	benign	-0.195	Destabilizing	0.973	D	0.627	neutral	None	None	None	None	N
A/I	0.2669	likely_benign	0.2289	benign	-0.303	Destabilizing	0.906	D	0.523	neutral	None	None	None	None	N
A/K	0.3665	ambiguous	0.3072	benign	-0.441	Destabilizing	0.404	N	0.483	neutral	None	None	None	None	N
A/L	0.1471	likely_benign	0.1361	benign	-0.303	Destabilizing	0.826	D	0.479	neutral	None	None	None	None	N
A/M	0.1839	likely_benign	0.159	benign	-0.415	Destabilizing	0.991	D	0.55	neutral	None	None	None	None	N
A/N	0.1191	likely_benign	0.1085	benign	-0.152	Destabilizing	0.704	D	0.566	neutral	None	None	None	None	N
A/P	0.4664	ambiguous	0.3724	ambiguous	-0.222	Destabilizing	0.879	D	0.519	neutral	N	0.47025242	None	None	N
A/Q	0.2479	likely_benign	0.2228	benign	-0.421	Destabilizing	0.704	D	0.515	neutral	None	None	None	None	N
A/R	0.3507	ambiguous	0.3019	benign	-0.023	Destabilizing	0.826	D	0.516	neutral	None	None	None	None	N
A/S	0.0755	likely_benign	0.0743	benign	-0.35	Destabilizing	0.338	N	0.467	neutral	N	0.47025242	None	None	N
A/T	0.0963	likely_benign	0.0889	benign	-0.428	Destabilizing	0.505	D	0.422	neutral	N	0.485491231	None	None	N
A/V	0.1393	likely_benign	0.1255	benign	-0.222	Destabilizing	0.505	D	0.426	neutral	N	0.478930618	None	None	N
A/W	0.6093	likely_pathogenic	0.5535	ambiguous	-0.942	Destabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	N
A/Y	0.3016	likely_benign	0.2611	benign	-0.6	Destabilizing	0.967	D	0.632	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.