NM_002181.4(IHH):c.2T>C (p.Met1Thr) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 5, 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:: RCV003696036.2

Allele description [Variation Report for NM_002181.4(IHH):c.2T>C (p.Met1Thr)]

NM_002181.4(IHH):c.2T>C (p.Met1Thr)

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.2T>C (p.Met1Thr)

HGVS:

NC_000002.12:g.219060466A>G
NG_016741.1:g.5051T>C
NG_016741.2:g.5455T>C
NM_002181.4:c.2T>CMANE SELECT
NP_002172.2:p.Met1Thr
NC_000002.11:g.219925188A>G

Protein change:

M1T

Molecular consequence:

NM_002181.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_002181.4:c.2T>C - 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
SCV004454053	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29155992, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004454053

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 5, 2023)

germline

clinical testing

PubMed (2)
[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

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Vasques GA, Funari MFA, Ferreira FM, Aza-Carmona M, Sentchordi-Montané L, Barraza-García J, Lerario AM, Yamamoto GL, Naslavsky MS, Duarte YAO, Bertola DR, Heath KE, Jorge AAL.

J Clin Endocrinol Metab. 2018 Feb 1;103(2):604-614. doi: 10.1210/jc.2017-02026.

PubMed [citation]

PMID:: 29155992

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004454053.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the IHH protein in which other variant(s) (p.Glu58Lys) have been determined to be pathogenic (PMID: 29155992). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with IHH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the IHH mRNA. The next in-frame methionine is located at codon 103.

#	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: Sep 29, 2024

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