TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27488	82687;82688;82689	chr2:178563670;178563669;178563668	chr2:179428397;179428396;179428395
N2AB	25847	77764;77765;77766	chr2:178563670;178563669;178563668	chr2:179428397;179428396;179428395
N2A	24920	74983;74984;74985	chr2:178563670;178563669;178563668	chr2:179428397;179428396;179428395
N2B	18423	55492;55493;55494	chr2:178563670;178563669;178563668	chr2:179428397;179428396;179428395
Novex-1	18548	55867;55868;55869	chr2:178563670;178563669;178563668	chr2:179428397;179428396;179428395
Novex-2	18615	56068;56069;56070	chr2:178563670;178563669;178563668	chr2:179428397;179428396;179428395
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-88
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1248
• 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
V/I	rs1704546804	None	0.055	N	0.512	0.065	0.434497104326	gnomAD-4.0.0	2.18942E-05	None	None	None	None	N	None	2.98757E-05	0	None	0	0	None	0	0	2.78836E-05	0	0
V/L	None	None	None	N	0.331	0.073	0.344251166708	gnomAD-4.0.0	6.84195E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-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
V/A	0.5738	likely_pathogenic	0.6732	pathogenic	-1.977	Destabilizing	0.104	N	0.697	prob.neutral	N	0.502416415	None	None	N
V/C	0.9024	likely_pathogenic	0.9254	pathogenic	-1.408	Destabilizing	0.968	D	0.766	deleterious	None	None	None	None	N
V/D	0.9972	likely_pathogenic	0.9978	pathogenic	-2.952	Highly Destabilizing	0.89	D	0.875	deleterious	None	None	None	None	N
V/E	0.9908	likely_pathogenic	0.9927	pathogenic	-2.624	Highly Destabilizing	0.667	D	0.821	deleterious	D	0.52967493	None	None	N
V/F	0.7945	likely_pathogenic	0.85	pathogenic	-1.109	Destabilizing	0.396	N	0.755	deleterious	None	None	None	None	N
V/G	0.8315	likely_pathogenic	0.8736	pathogenic	-2.609	Highly Destabilizing	0.667	D	0.836	deleterious	N	0.511735259	None	None	N
V/H	0.9968	likely_pathogenic	0.9978	pathogenic	-2.68	Highly Destabilizing	0.968	D	0.865	deleterious	None	None	None	None	N
V/I	0.0969	likely_benign	0.0978	benign	-0.151	Destabilizing	0.055	N	0.512	neutral	N	0.468994131	None	None	N
V/K	0.9927	likely_pathogenic	0.9945	pathogenic	-1.601	Destabilizing	0.726	D	0.799	deleterious	None	None	None	None	N
V/L	0.2016	likely_benign	0.2212	benign	-0.151	Destabilizing	None	N	0.331	neutral	N	0.390983559	None	None	N
V/M	0.4584	ambiguous	0.5476	ambiguous	-0.372	Destabilizing	0.396	N	0.696	prob.neutral	None	None	None	None	N
V/N	0.9892	likely_pathogenic	0.9919	pathogenic	-2.29	Highly Destabilizing	0.89	D	0.877	deleterious	None	None	None	None	N
V/P	0.9867	likely_pathogenic	0.987	pathogenic	-0.738	Destabilizing	0.89	D	0.839	deleterious	None	None	None	None	N
V/Q	0.9862	likely_pathogenic	0.9906	pathogenic	-1.894	Destabilizing	0.89	D	0.842	deleterious	None	None	None	None	N
V/R	0.9866	likely_pathogenic	0.9898	pathogenic	-1.833	Destabilizing	0.726	D	0.876	deleterious	None	None	None	None	N
V/S	0.9346	likely_pathogenic	0.9583	pathogenic	-2.813	Highly Destabilizing	0.726	D	0.801	deleterious	None	None	None	None	N
V/T	0.8242	likely_pathogenic	0.8739	pathogenic	-2.312	Highly Destabilizing	0.272	N	0.681	prob.neutral	None	None	None	None	N
V/W	0.9973	likely_pathogenic	0.9982	pathogenic	-1.742	Destabilizing	0.968	D	0.85	deleterious	None	None	None	None	N
V/Y	0.9876	likely_pathogenic	0.9914	pathogenic	-1.319	Destabilizing	0.726	D	0.763	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.