TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22875	68848;68849;68850	chr2:178577803;178577802;178577801	chr2:179442530;179442529;179442528
N2AB	21234	63925;63926;63927	chr2:178577803;178577802;178577801	chr2:179442530;179442529;179442528
N2A	20307	61144;61145;61146	chr2:178577803;178577802;178577801	chr2:179442530;179442529;179442528
N2B	13810	41653;41654;41655	chr2:178577803;178577802;178577801	chr2:179442530;179442529;179442528
Novex-1	13935	42028;42029;42030	chr2:178577803;178577802;178577801	chr2:179442530;179442529;179442528
Novex-2	14002	42229;42230;42231	chr2:178577803;178577802;178577801	chr2:179442530;179442529;179442528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-54
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0948
• 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
G/E	None	None	1.0	N	0.887	0.674	0.539970339866	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
G/A	0.4864	ambiguous	0.5047	ambiguous	-0.761	Destabilizing	1.0	D	0.599	neutral	N	0.506837415	None	None	N
G/C	0.7559	likely_pathogenic	0.7897	pathogenic	-1.028	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/D	0.9665	likely_pathogenic	0.974	pathogenic	-1.627	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/E	0.9739	likely_pathogenic	0.9792	pathogenic	-1.601	Destabilizing	1.0	D	0.887	deleterious	N	0.493492873	None	None	N
G/F	0.9835	likely_pathogenic	0.9853	pathogenic	-0.898	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
G/H	0.9659	likely_pathogenic	0.9704	pathogenic	-1.55	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/I	0.981	likely_pathogenic	0.985	pathogenic	-0.126	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/K	0.992	likely_pathogenic	0.9929	pathogenic	-1.207	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
G/L	0.9758	likely_pathogenic	0.9808	pathogenic	-0.126	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/M	0.9756	likely_pathogenic	0.9803	pathogenic	-0.226	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/N	0.9133	likely_pathogenic	0.9365	pathogenic	-1.083	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
G/P	0.9996	likely_pathogenic	0.9995	pathogenic	-0.295	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/Q	0.9597	likely_pathogenic	0.9638	pathogenic	-1.155	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/R	0.9661	likely_pathogenic	0.9704	pathogenic	-1.063	Destabilizing	1.0	D	0.874	deleterious	N	0.505823457	None	None	N
G/S	0.3262	likely_benign	0.3347	benign	-1.379	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
G/T	0.84	likely_pathogenic	0.8593	pathogenic	-1.267	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/V	0.9526	likely_pathogenic	0.9606	pathogenic	-0.295	Destabilizing	1.0	D	0.889	deleterious	D	0.559682149	None	None	N
G/W	0.9728	likely_pathogenic	0.975	pathogenic	-1.43	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
G/Y	0.9624	likely_pathogenic	0.9693	pathogenic	-0.939	Destabilizing	1.0	D	0.847	deleterious	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.