NM_002181.4(IHH):c.283G>A (p.Glu95Lys) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003555989.1

Allele description [Variation Report for NM_002181.4(IHH):c.283G>A (p.Glu95Lys)]

NM_002181.4(IHH):c.283G>A (p.Glu95Lys)

Gene:

IHH:Indian hedgehog signaling molecule [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_002181.4(IHH):c.283G>A (p.Glu95Lys)

HGVS:

NC_000002.12:g.219060185C>T
NG_016741.1:g.5332G>A
NM_002181.4:c.283G>AMANE SELECT
NP_002172.2:p.Glu95Lys
NC_000002.11:g.219924907C>T
Q14623:p.Glu95Lys

Protein change:

E95K; GLU95LYS

Links:

UniProtKB: Q14623#VAR_015982; OMIM: 600726.0001; dbSNP: rs121917852

NCBI 1000 Genomes Browser:

rs121917852

Molecular consequence:

NM_002181.4:c.283G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293976	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19252479, 11455389, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293976

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range.

Gao B, Hu J, Stricker S, Cheung M, Ma G, Law KF, Witte F, Briscoe J, Mundlos S, He L, Cheah KS, Chan D.

Nature. 2009 Apr 30;458(7242):1196-200. doi: 10.1038/nature07862. Epub 2009 Mar 1.

PubMed [citation]

PMID:: 19252479

Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1.

Gao B, Guo J, She C, Shu A, Yang M, Tan Z, Yang X, Guo S, Feng G, He L.

Nat Genet. 2001 Aug;28(4):386-8.

PubMed [citation]

PMID:: 11455389

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004293976.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects IHH function (PMID: 19252479). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IHH protein function. ClinVar contains an entry for this variant (Variation ID: 8866). This missense change has been observed in individuals with brachydactyly (PMID: 11455389; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 95 of the IHH protein (p.Glu95Lys).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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