TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9122	27589;27590;27591	chr2:178712558;178712557;178712556	chr2:179577285;179577284;179577283
N2AB	8805	26638;26639;26640	chr2:178712558;178712557;178712556	chr2:179577285;179577284;179577283
N2A	7878	23857;23858;23859	chr2:178712558;178712557;178712556	chr2:179577285;179577284;179577283
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-77
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.4957
• 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
S/G	rs2076813561	None	0.454	N	0.311	0.286	0.225902525712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
S/A	0.091	likely_benign	0.0859	benign	-0.189	Destabilizing	0.688	D	0.416	neutral	None	None	None	None	I
S/C	0.124	likely_benign	0.1297	benign	-0.362	Destabilizing	0.997	D	0.428	neutral	N	0.520891016	None	None	I
S/D	0.4129	ambiguous	0.4579	ambiguous	0.541	Stabilizing	0.728	D	0.309	neutral	None	None	None	None	I
S/E	0.5088	ambiguous	0.5192	ambiguous	0.518	Stabilizing	0.728	D	0.301	neutral	None	None	None	None	I
S/F	0.2309	likely_benign	0.2139	benign	-0.649	Destabilizing	0.991	D	0.445	neutral	None	None	None	None	I
S/G	0.1043	likely_benign	0.1154	benign	-0.362	Destabilizing	0.454	N	0.311	neutral	N	0.508520753	None	None	I
S/H	0.2908	likely_benign	0.3177	benign	-0.658	Destabilizing	0.974	D	0.394	neutral	None	None	None	None	I
S/I	0.1575	likely_benign	0.1664	benign	0.143	Stabilizing	0.934	D	0.437	neutral	D	0.526978934	None	None	I
S/K	0.563	ambiguous	0.5935	pathogenic	-0.139	Destabilizing	0.728	D	0.307	neutral	None	None	None	None	I
S/L	0.1204	likely_benign	0.1124	benign	0.143	Stabilizing	0.842	D	0.407	neutral	None	None	None	None	I
S/M	0.2259	likely_benign	0.2258	benign	-0.098	Destabilizing	0.998	D	0.395	neutral	None	None	None	None	I
S/N	0.1231	likely_benign	0.1468	benign	-0.182	Destabilizing	0.012	N	0.159	neutral	N	0.521783758	None	None	I
S/P	0.3582	ambiguous	0.3711	ambiguous	0.065	Stabilizing	0.974	D	0.394	neutral	None	None	None	None	I
S/Q	0.4126	ambiguous	0.4399	ambiguous	-0.237	Destabilizing	0.142	N	0.251	neutral	None	None	None	None	I
S/R	0.4165	ambiguous	0.4525	ambiguous	-0.049	Destabilizing	0.876	D	0.354	neutral	N	0.483895584	None	None	I
S/T	0.0882	likely_benign	0.0834	benign	-0.208	Destabilizing	0.051	N	0.227	neutral	N	0.466255762	None	None	I
S/V	0.175	likely_benign	0.1709	benign	0.065	Stabilizing	0.842	D	0.405	neutral	None	None	None	None	I
S/W	0.3765	ambiguous	0.3771	ambiguous	-0.745	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	I
S/Y	0.1888	likely_benign	0.1906	benign	-0.379	Destabilizing	0.991	D	0.444	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.