TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22933	69022;69023;69024	chr2:178577629;178577628;178577627	chr2:179442356;179442355;179442354
N2AB	21292	64099;64100;64101	chr2:178577629;178577628;178577627	chr2:179442356;179442355;179442354
N2A	20365	61318;61319;61320	chr2:178577629;178577628;178577627	chr2:179442356;179442355;179442354
N2B	13868	41827;41828;41829	chr2:178577629;178577628;178577627	chr2:179442356;179442355;179442354
Novex-1	13993	42202;42203;42204	chr2:178577629;178577628;178577627	chr2:179442356;179442355;179442354
Novex-2	14060	42403;42404;42405	chr2:178577629;178577628;178577627	chr2:179442356;179442355;179442354
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-54
• Domain position: 93
• Structural Position: 125
• Q(SASA): 0.535
• 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
E/K	None	None	0.058	N	0.321	0.185	0.321951552304	gnomAD-4.0.0	1.59698E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86566E-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
E/A	0.0868	likely_benign	0.0855	benign	-0.095	Destabilizing	None	N	0.197	neutral	D	0.527493435	None	None	I
E/C	0.5896	likely_pathogenic	0.6135	pathogenic	-0.035	Destabilizing	0.869	D	0.341	neutral	None	None	None	None	I
E/D	0.0631	likely_benign	0.0624	benign	-0.206	Destabilizing	None	N	0.172	neutral	N	0.462308593	None	None	I
E/F	0.6793	likely_pathogenic	0.7023	pathogenic	-0.119	Destabilizing	0.637	D	0.41	neutral	None	None	None	None	I
E/G	0.0489	likely_benign	0.0449	benign	-0.228	Destabilizing	None	N	0.168	neutral	N	0.445896346	None	None	I
E/H	0.3455	ambiguous	0.3591	ambiguous	0.374	Stabilizing	0.366	N	0.298	neutral	None	None	None	None	I
E/I	0.3313	likely_benign	0.3548	ambiguous	0.201	Stabilizing	0.366	N	0.487	neutral	None	None	None	None	I
E/K	0.1161	likely_benign	0.1267	benign	0.476	Stabilizing	0.058	N	0.321	neutral	N	0.521874184	None	None	I
E/L	0.3422	ambiguous	0.3549	ambiguous	0.201	Stabilizing	0.075	N	0.489	neutral	None	None	None	None	I
E/M	0.4133	ambiguous	0.4186	ambiguous	0.1	Stabilizing	0.869	D	0.363	neutral	None	None	None	None	I
E/N	0.1286	likely_benign	0.1311	benign	0.263	Stabilizing	0.039	N	0.216	neutral	None	None	None	None	I
E/P	0.2414	likely_benign	0.2424	benign	0.121	Stabilizing	0.366	N	0.429	neutral	None	None	None	None	I
E/Q	0.1239	likely_benign	0.1244	benign	0.272	Stabilizing	0.058	N	0.389	neutral	N	0.489826478	None	None	I
E/R	0.19	likely_benign	0.2025	benign	0.676	Stabilizing	0.221	N	0.311	neutral	None	None	None	None	I
E/S	0.0943	likely_benign	0.0915	benign	0.101	Stabilizing	0.016	N	0.297	neutral	None	None	None	None	I
E/T	0.1449	likely_benign	0.1457	benign	0.214	Stabilizing	0.075	N	0.297	neutral	None	None	None	None	I
E/V	0.1916	likely_benign	0.2067	benign	0.121	Stabilizing	0.058	N	0.412	neutral	N	0.512102695	None	None	I
E/W	0.7833	likely_pathogenic	0.8021	pathogenic	-0.051	Destabilizing	0.869	D	0.396	neutral	None	None	None	None	I
E/Y	0.482	ambiguous	0.5192	ambiguous	0.113	Stabilizing	0.637	D	0.403	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.