NM_004006.3(DMD):c.2330T>C (p.Leu777Pro) AND Duchenne muscular dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 4, 2024
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:: RCV001852148.5

Allele description [Variation Report for NM_004006.3(DMD):c.2330T>C (p.Leu777Pro)]

NM_004006.3(DMD):c.2330T>C (p.Leu777Pro)

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.2330T>C (p.Leu777Pro)

HGVS:

NC_000023.11:g.32501805A>G
NG_012232.1:g.842805T>C
NM_000109.4:c.2306T>C
NM_004006.3:c.2330T>CMANE SELECT
NM_004009.3:c.2318T>C
NM_004010.3:c.1961T>C
NP_000100.3:p.Leu769Pro
NP_003997.1:p.Leu777Pro
NP_003997.2:p.Leu777Pro
NP_004000.1:p.Leu773Pro
NP_004001.1:p.Leu654Pro
LRG_199t1:c.2330T>C
LRG_199:g.842805T>C
LRG_199p1:p.Leu777Pro
NC_000023.10:g.32519922A>G
NM_004006.2:c.2330T>C

Protein change:

L654P

Links:

dbSNP: rs794727226

NCBI 1000 Genomes Browser:

rs794727226

Molecular consequence:

NM_000109.4:c.2306T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004006.3:c.2330T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004009.3:c.2318T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004010.3:c.1961T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Duchenne muscular dystrophy (DMD)
Synonyms:: Muscular dystrophy, pseudohypertrophic progressive, Duchenne type
Identifiers:: MONDO: MONDO:0010679; MedGen: C0013264; Orphanet: 98896; OMIM: 310200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002317536	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 4, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29365344, 33644936, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002317536

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 4, 2024)

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

Dystrophinopathy muscle biopsies in the genetic testing ERA: One center's data.

Carlson CR, Moore SA, Mathews KD.

Muscle Nerve. 2018 Jan 24. doi: 10.1002/mus.26083. [Epub ahead of print]

PubMed [citation]

PMID:: 29365344
PMCID:: PMC6057846

A single NGS-based assay covering the entire genomic sequence of the DMD gene facilitates diagnostic and newborn screening confirmatory testing.

Nallamilli BRR, Chaubey A, Valencia CA, Stansberry L, Behlmann AM, Ma Z, Mathur A, Shenoy S, Ganapathy V, Jagannathan L, Ramachander V, Ferlini A, Bean L, Hegde M.

Hum Mutat. 2021 May;42(5):626-638. doi: 10.1002/humu.24191. Epub 2021 Mar 19.

PubMed [citation]

PMID:: 33644936

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002317536.3

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 777 of the DMD protein (p.Leu777Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Duchenne muscular dystrophy (PMID: 29365344, 33644936). ClinVar contains an entry for this variant (Variation ID: 194952). 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 not expected to disrupt DMD protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Mar 16, 2024

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