TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27038	81337;81338;81339	chr2:178565020;178565019;178565018	chr2:179429747;179429746;179429745
N2AB	25397	76414;76415;76416	chr2:178565020;178565019;178565018	chr2:179429747;179429746;179429745
N2A	24470	73633;73634;73635	chr2:178565020;178565019;178565018	chr2:179429747;179429746;179429745
N2B	17973	54142;54143;54144	chr2:178565020;178565019;178565018	chr2:179429747;179429746;179429745
Novex-1	18098	54517;54518;54519	chr2:178565020;178565019;178565018	chr2:179429747;179429746;179429745
Novex-2	18165	54718;54719;54720	chr2:178565020;178565019;178565018	chr2:179429747;179429746;179429745
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-84
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6491
• 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/Q	rs1705165045	None	0.036	N	0.273	0.151	0.136095386433	gnomAD-4.0.0	2.05323E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69879E-06	0	0
K/R	None	None	0.004	N	0.27	0.132	0.17948927462	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	0.425	ambiguous	0.3639	ambiguous	-0.288	Destabilizing	0.25	N	0.419	neutral	None	None	None	None	N
K/C	0.6885	likely_pathogenic	0.6165	pathogenic	-0.522	Destabilizing	0.992	D	0.41	neutral	None	None	None	None	N
K/D	0.7509	likely_pathogenic	0.7127	pathogenic	0.208	Stabilizing	0.617	D	0.435	neutral	None	None	None	None	N
K/E	0.2944	likely_benign	0.2665	benign	0.268	Stabilizing	0.379	N	0.421	neutral	N	0.478576406	None	None	N
K/F	0.8473	likely_pathogenic	0.7841	pathogenic	-0.368	Destabilizing	0.92	D	0.398	neutral	None	None	None	None	N
K/G	0.6263	likely_pathogenic	0.5459	ambiguous	-0.536	Destabilizing	0.617	D	0.447	neutral	None	None	None	None	N
K/H	0.3328	likely_benign	0.2893	benign	-0.729	Destabilizing	0.977	D	0.403	neutral	None	None	None	None	N
K/I	0.3806	ambiguous	0.3192	benign	0.306	Stabilizing	0.681	D	0.381	neutral	N	0.463225739	None	None	N
K/L	0.4167	ambiguous	0.3501	ambiguous	0.306	Stabilizing	0.447	N	0.441	neutral	None	None	None	None	N
K/M	0.2888	likely_benign	0.2461	benign	-0.002	Destabilizing	0.92	D	0.405	neutral	None	None	None	None	N
K/N	0.5183	ambiguous	0.4432	ambiguous	-0.115	Destabilizing	0.81	D	0.402	neutral	N	0.470029339	None	None	N
K/P	0.8504	likely_pathogenic	0.8265	pathogenic	0.137	Stabilizing	0.92	D	0.421	neutral	None	None	None	None	N
K/Q	0.1484	likely_benign	0.1334	benign	-0.174	Destabilizing	0.036	N	0.273	neutral	N	0.510054107	None	None	N
K/R	0.0963	likely_benign	0.0894	benign	-0.161	Destabilizing	0.004	N	0.27	neutral	N	0.500663832	None	None	N
K/S	0.5192	ambiguous	0.4493	ambiguous	-0.69	Destabilizing	0.447	N	0.389	neutral	None	None	None	None	N
K/T	0.1746	likely_benign	0.1523	benign	-0.447	Destabilizing	0.016	N	0.262	neutral	N	0.465975255	None	None	N
K/V	0.3432	ambiguous	0.2888	benign	0.137	Stabilizing	0.012	N	0.3	neutral	None	None	None	None	N
K/W	0.8585	likely_pathogenic	0.8003	pathogenic	-0.346	Destabilizing	0.992	D	0.519	neutral	None	None	None	None	N
K/Y	0.7344	likely_pathogenic	0.6685	pathogenic	-0.007	Destabilizing	0.972	D	0.417	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.