TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19116	57571;57572;57573	chr2:178597736;178597735;178597734	chr2:179462463;179462462;179462461
N2AB	17475	52648;52649;52650	chr2:178597736;178597735;178597734	chr2:179462463;179462462;179462461
N2A	16548	49867;49868;49869	chr2:178597736;178597735;178597734	chr2:179462463;179462462;179462461
N2B	10051	30376;30377;30378	chr2:178597736;178597735;178597734	chr2:179462463;179462462;179462461
Novex-1	10176	30751;30752;30753	chr2:178597736;178597735;178597734	chr2:179462463;179462462;179462461
Novex-2	10243	30952;30953;30954	chr2:178597736;178597735;178597734	chr2:179462463;179462462;179462461
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-117
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.4397
• 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
V/M	rs2052100792	None	1.0	D	0.774	0.525	0.805721141949	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/M	rs2052100792	None	1.0	D	0.774	0.525	0.805721141949	gnomAD-4.0.0	6.57765E-06	None	None	None	None	I	None	0	6.55222E-05	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
V/A	0.748	likely_pathogenic	0.8349	pathogenic	-0.617	Destabilizing	0.999	D	0.615	neutral	N	0.521562832	None	None	I
V/C	0.8945	likely_pathogenic	0.9118	pathogenic	-0.72	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/D	0.9892	likely_pathogenic	0.9941	pathogenic	0.065	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
V/E	0.9631	likely_pathogenic	0.9781	pathogenic	-0.007	Destabilizing	1.0	D	0.81	deleterious	D	0.597837834	None	None	I
V/F	0.4711	ambiguous	0.606	pathogenic	-0.616	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
V/G	0.8823	likely_pathogenic	0.9286	pathogenic	-0.811	Destabilizing	1.0	D	0.823	deleterious	D	0.581818473	None	None	I
V/H	0.9688	likely_pathogenic	0.9831	pathogenic	-0.408	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
V/I	0.0839	likely_benign	0.0817	benign	-0.237	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	I
V/K	0.959	likely_pathogenic	0.9756	pathogenic	-0.467	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
V/L	0.4547	ambiguous	0.5365	ambiguous	-0.237	Destabilizing	0.997	D	0.671	neutral	D	0.538444762	None	None	I
V/M	0.4686	ambiguous	0.5549	ambiguous	-0.359	Destabilizing	1.0	D	0.774	deleterious	D	0.597434225	None	None	I
V/N	0.9556	likely_pathogenic	0.9731	pathogenic	-0.234	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/P	0.9871	likely_pathogenic	0.9918	pathogenic	-0.327	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
V/Q	0.9361	likely_pathogenic	0.9603	pathogenic	-0.397	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
V/R	0.9332	likely_pathogenic	0.9606	pathogenic	-0.075	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/S	0.8817	likely_pathogenic	0.9263	pathogenic	-0.717	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
V/T	0.745	likely_pathogenic	0.7988	pathogenic	-0.673	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I
V/W	0.9796	likely_pathogenic	0.989	pathogenic	-0.719	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/Y	0.905	likely_pathogenic	0.9425	pathogenic	-0.409	Destabilizing	1.0	D	0.814	deleterious	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.