TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15124	45595;45596;45597	chr2:178621348;178621347;178621346	chr2:179486075;179486074;179486073
N2AB	13483	40672;40673;40674	chr2:178621348;178621347;178621346	chr2:179486075;179486074;179486073
N2A	12556	37891;37892;37893	chr2:178621348;178621347;178621346	chr2:179486075;179486074;179486073
N2B	6059	18400;18401;18402	chr2:178621348;178621347;178621346	chr2:179486075;179486074;179486073
Novex-1	6184	18775;18776;18777	chr2:178621348;178621347;178621346	chr2:179486075;179486074;179486073
Novex-2	6251	18976;18977;18978	chr2:178621348;178621347;178621346	chr2:179486075;179486074;179486073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-103
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2977
• 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/A	None	None	0.007	N	0.109	0.053	0.194818534648	gnomAD-4.0.0	1.59693E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86466E-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	0.0822	likely_benign	0.0791	benign	-0.582	Destabilizing	0.007	N	0.109	neutral	N	0.488570868	None	None	N
S/C	0.1896	likely_benign	0.1703	benign	-0.381	Destabilizing	0.992	D	0.355	neutral	None	None	None	None	N
S/D	0.5494	ambiguous	0.5662	pathogenic	0.224	Stabilizing	0.617	D	0.312	neutral	None	None	None	None	N
S/E	0.5641	likely_pathogenic	0.5775	pathogenic	0.197	Stabilizing	0.617	D	0.319	neutral	None	None	None	None	N
S/F	0.2887	likely_benign	0.2893	benign	-0.908	Destabilizing	0.92	D	0.453	neutral	None	None	None	None	N
S/G	0.1547	likely_benign	0.146	benign	-0.794	Destabilizing	0.25	N	0.337	neutral	None	None	None	None	N
S/H	0.4771	ambiguous	0.4657	ambiguous	-1.236	Destabilizing	0.972	D	0.361	neutral	None	None	None	None	N
S/I	0.2448	likely_benign	0.2639	benign	-0.14	Destabilizing	0.739	D	0.423	neutral	None	None	None	None	N
S/K	0.7766	likely_pathogenic	0.7912	pathogenic	-0.537	Destabilizing	0.447	N	0.335	neutral	None	None	None	None	N
S/L	0.1264	likely_benign	0.1272	benign	-0.14	Destabilizing	0.379	N	0.422	neutral	N	0.504011078	None	None	N
S/M	0.2511	likely_benign	0.2424	benign	0.026	Stabilizing	0.92	D	0.364	neutral	None	None	None	None	N
S/N	0.2023	likely_benign	0.1998	benign	-0.432	Destabilizing	0.617	D	0.329	neutral	None	None	None	None	N
S/P	0.9181	likely_pathogenic	0.9228	pathogenic	-0.254	Destabilizing	0.896	D	0.357	neutral	D	0.601225419	None	None	N
S/Q	0.5483	ambiguous	0.5423	ambiguous	-0.555	Destabilizing	0.85	D	0.36	neutral	None	None	None	None	N
S/R	0.6952	likely_pathogenic	0.7149	pathogenic	-0.435	Destabilizing	0.005	N	0.216	neutral	None	None	None	None	N
S/T	0.081	likely_benign	0.0812	benign	-0.491	Destabilizing	0.002	N	0.108	neutral	N	0.463668937	None	None	N
S/V	0.2235	likely_benign	0.2296	benign	-0.254	Destabilizing	0.447	N	0.42	neutral	None	None	None	None	N
S/W	0.552	ambiguous	0.5538	ambiguous	-0.902	Destabilizing	0.992	D	0.513	neutral	None	None	None	None	N
S/Y	0.286	likely_benign	0.2829	benign	-0.624	Destabilizing	0.972	D	0.45	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.