TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20864	62815;62816;62817	chr2:178589135;178589134;178589133	chr2:179453862;179453861;179453860
N2AB	19223	57892;57893;57894	chr2:178589135;178589134;178589133	chr2:179453862;179453861;179453860
N2A	18296	55111;55112;55113	chr2:178589135;178589134;178589133	chr2:179453862;179453861;179453860
N2B	11799	35620;35621;35622	chr2:178589135;178589134;178589133	chr2:179453862;179453861;179453860
Novex-1	11924	35995;35996;35997	chr2:178589135;178589134;178589133	chr2:179453862;179453861;179453860
Novex-2	11991	36196;36197;36198	chr2:178589135;178589134;178589133	chr2:179453862;179453861;179453860
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-39
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6097
• 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
K/E	None	None	0.791	N	0.423	0.159	0.21279746466	gnomAD-4.0.0	1.59304E-06	None	None	None	None	N	None	0	0	None	0	2.78242E-05	None	0	0	0	0	0
K/N	None	None	0.976	N	0.383	0.186	0.177238962908	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.7012	likely_pathogenic	0.702	pathogenic	-0.092	Destabilizing	0.338	N	0.449	neutral	None	None	None	None	N
K/C	0.7945	likely_pathogenic	0.7985	pathogenic	-0.282	Destabilizing	0.995	D	0.345	neutral	None	None	None	None	N
K/D	0.9636	likely_pathogenic	0.9668	pathogenic	0.252	Stabilizing	0.982	D	0.43	neutral	None	None	None	None	N
K/E	0.614	likely_pathogenic	0.653	pathogenic	0.27	Stabilizing	0.791	D	0.423	neutral	N	0.464112358	None	None	N
K/F	0.9379	likely_pathogenic	0.938	pathogenic	-0.233	Destabilizing	0.946	D	0.406	neutral	None	None	None	None	N
K/G	0.9012	likely_pathogenic	0.9042	pathogenic	-0.315	Destabilizing	0.834	D	0.377	neutral	None	None	None	None	N
K/H	0.6469	likely_pathogenic	0.6432	pathogenic	-0.581	Destabilizing	0.995	D	0.359	neutral	None	None	None	None	N
K/I	0.3816	ambiguous	0.3959	ambiguous	0.421	Stabilizing	0.032	N	0.278	neutral	None	None	None	None	N
K/L	0.6383	likely_pathogenic	0.6392	pathogenic	0.421	Stabilizing	0.338	N	0.443	neutral	None	None	None	None	N
K/M	0.4323	ambiguous	0.439	ambiguous	0.251	Stabilizing	0.93	D	0.369	neutral	N	0.464619337	None	None	N
K/N	0.8775	likely_pathogenic	0.8835	pathogenic	0.207	Stabilizing	0.976	D	0.383	neutral	N	0.497903168	None	None	N
K/P	0.9036	likely_pathogenic	0.9248	pathogenic	0.279	Stabilizing	0.982	D	0.442	neutral	None	None	None	None	N
K/Q	0.3194	likely_benign	0.3247	benign	0.017	Stabilizing	0.976	D	0.445	neutral	N	0.458035972	None	None	N
K/R	0.098	likely_benign	0.0972	benign	-0.027	Destabilizing	0.92	D	0.493	neutral	N	0.408358599	None	None	N
K/S	0.8331	likely_pathogenic	0.8443	pathogenic	-0.377	Destabilizing	0.834	D	0.327	neutral	None	None	None	None	N
K/T	0.3494	ambiguous	0.3421	ambiguous	-0.197	Destabilizing	0.651	D	0.422	neutral	N	0.480240127	None	None	N
K/V	0.3369	likely_benign	0.3532	ambiguous	0.279	Stabilizing	0.003	N	0.124	neutral	None	None	None	None	N
K/W	0.9584	likely_pathogenic	0.9546	pathogenic	-0.184	Destabilizing	0.995	D	0.553	neutral	None	None	None	None	N
K/Y	0.8826	likely_pathogenic	0.8887	pathogenic	0.16	Stabilizing	0.982	D	0.423	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.